Supplementary File FN Clarivate Analytics Web of Science VR 1.0 PT J AU Nilson, R Krutzke, L Wienen, F Rojewski, M Zeplin, PH Funk, W Schrezenmeier, H Kochanek, S Kritzinger, A AF Nilson, Robin Krutzke, Lea Wienen, Frederik Rojewski, Markus Zeplin, Philip Helge Funk, Wolfgang Schrezenmeier, Hubert Kochanek, Stefan Kritzinger, Astrid TI Evaluation of Human Mesenchymal Stromal Cells as Carriers for the Delivery of Oncolytic HAdV-5 to Head and Neck Squamous Cell Carcinomas SO VIRUSES-BASEL LA English DT Article DE human mesenchymal stromal cells; mesenchymal stem cells; carrier cells; human head and neck squamous cell carcinoma; migration; oncolytic adenovirus ID ADENOVIRUS TYPE 5; STEM-CELLS; INTERNATIONAL-SOCIETY; CAR-BINDING; IN-VIVO; RECEPTOR; IDENTIFICATION; THERAPY; VECTORS; PROTEIN AB Human multipotent mesenchymal stromal cells (hMSCs) are of significant therapeutic interest due to their ability to deliver oncolytic adenoviruses to tumors. This approach is also investigated for targeting head and neck squamous cell carcinomas (HNSCCs). HAdV-5-HexPos3, a recently reported capsid-modified vector based on human adenovirus type 5 (HAdV-5), showed strongly improved infection of both hMSCs and the HNSCC cell line UM-SCC-11B. Given that, we generated life cycle-unmodified and -modified replication-competent HAdV-5-HexPos3 vector variants and analyzed their replication within bone marrow- and adipose tissue-derived hMSCs. Efficient replication was detected for both life cycle-unmodified and -modified vectors. Moreover, we analyzed the migration of vector-carrying hMSCs toward different HNSCCs. Although migration of hMSCs to HNSCC cell lines was confirmed in vitro, no homing of hMSCs to HNSCC xenografts was observed in vivo in mice and in ovo in a chorioallantoic membrane model. Taken together, our data suggest that HAdV-5-HexPos3 is a potent candidate for hMSC-based oncolytic therapy of HNSCCs. However, it also emphasizes the importance of generating optimized in vivo models for the evaluation of hMSC as carrier cells. C1 [Nilson, Robin; Krutzke, Lea; Wienen, Frederik; Kochanek, Stefan; Kritzinger, Astrid] Univ Med Ctr Ulm, Dept Gene Therapy, D-89081 Ulm, Germany. [Rojewski, Markus; Schrezenmeier, Hubert] Univ Med Ctr Ulm, Inst Transfus Med, D-89081 Ulm, Germany. [Rojewski, Markus; Schrezenmeier, Hubert] German Red Cross Blood Donat Serv, Inst Clin Transfus Med & Immunogenet Ulm, D-89081 Ulm, Germany. [Zeplin, Philip Helge] Privatklin Plast & Asthet Chirurg, Schlosspark Klin Ludwigsburg, D-71638 Ludwigsburg, Germany. [Funk, Wolfgang] Schonheitsklin Dr Funk, Schonheitsklin Dr, D-81739 Munich, Germany. C3 Ulm University; Ulm University RP Kochanek, S; Kritzinger, A (corresponding author), Univ Med Ctr Ulm, Dept Gene Therapy, D-89081 Ulm, Germany. EM stefan.kochanek@uni-ulm.de; astrid.kritzinger@uni-ulm.de OI Kochanek, Stefan/0000-0001-7494-1602; Krutzke, Lea/0000-0002-4092-4131 FU German Federal Ministry of Education and Research (BMBF); Federal States of Germany Grant "Innovative Hochschule" [FKZ 3IHS024D]; 7th Framework Programme of the European Commission (project title REBORNE) [241879]; European Commission [643809]; Sanitaetsakademie der Bundeswehr [E/U2AD/ID018/IF557] FX The work was supported by the German Federal Ministry of Education and Research (BMBF) and the Federal States of Germany Grant "Innovative Hochschule" (FKZ 3IHS024D). Parts of this research were funded by the 7th Framework Programme of the European Commission (project title REBORNE, grant agreement number 241879), the H2020 Programme of the European Commission (project title ADIPOA-2, grant agreement number 643809), and by the Sanitaetsakademie der Bundeswehr E/U2AD/ID018/IF557. The materials presented and views expressed here are the responsibility of the authors only. The EU Commission takes no responsibility for any use made of the information set out. 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Published, gold DA 2025-10-02 ER PT J AU Nilson, R Lübbers, O Weiss, L Singh, K Scharffetter-Kochanek, K Rojewski, M Schrezenmeier, H Zeplin, PH Funk, W Krutzke, L Kochanek, S Kritzinger, A AF Nilson, Robin Luebbers, Olivia Weiss, Linus Singh, Karmveer Scharffetter-Kochanek, Karin Rojewski, Markus Schrezenmeier, Hubert Zeplin, Philip Helge Funk, Wolfgang Krutzke, Lea Kochanek, Stefan Kritzinger, Astrid TI Transduction Enhancers Enable Efficient Human Adenovirus Type 5-Mediated Gene Transfer into Human Multipotent Mesenchymal Stromal Cells SO VIRUSES-BASEL LA English DT Article DE hMSC; mesenchymal stromal cells; mesenchymal stem cells; adenovirus; gene therapy; transduction enhancer; viral vectors; good manufacturing practice; GMP ID STEM-CELLS; IN-VITRO; INTERNATIONAL-SOCIETY; ONCOLYTIC ADENOVIRUS; ENDOTHELIAL-CELLS; BINDING; TSG-6; MIGRATION; INFECTION; RECEPTOR AB Human multipotent mesenchymal stromal cells (hMSCs) are currently developed as cell therapeutics for different applications, including regenerative medicine, immune modulation, and cancer treatment. The biological properties of hMSCs can be further modulated by genetic engineering. Viral vectors based on human adenovirus type 5 (HAdV-5) belong to the most frequently used vector types for genetic modification of human cells in vitro and in vivo. However, due to a lack of the primary attachment receptor coxsackievirus and adenovirus receptor (CAR) in hMSCs, HAdV-5 vectors are currently not suitable for transduction of this cell type without capsid modification. Here we present several transduction enhancers that strongly enhance HAdV-5-mediated gene transfer into both bone marrow- and adipose tissue-derived hMSCs. Polybrene, poly-l-lysine, human lactoferrin, human blood coagulation factor X, spermine, and spermidine enabled high eGFP expression levels in hMSCs. Importantly, hMSCs treated with enhancers were not affected in their migration behavior, which is a key requisite for many therapeutic applications. Exemplary, strongly increased expression of tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6) (a secreted model therapeutic protein) was achieved by enhancer-facilitated HAdV-5 transduction. Thus, enhancer-mediated HAdV-5 vector transduction is a valuable method for the engineering of hMSCs, which can be further exploited for the development of innovative hMSC therapeutics. C1 [Nilson, Robin; Luebbers, Olivia; Weiss, Linus; Krutzke, Lea; Kochanek, Stefan; Kritzinger, Astrid] Univ Med Ctr Ulm, Dept Gene Therapy, D-89081 Ulm, Germany. [Singh, Karmveer; Scharffetter-Kochanek, Karin] Univ Med Ctr Ulm, Dept Dermatol & Allergol, D-89081 Ulm, Germany. [Rojewski, Markus; Schrezenmeier, Hubert] Univ Med Ctr Ulm, Inst Transfus Med, D-89081 Ulm, Germany. [Rojewski, Markus; Schrezenmeier, Hubert] Inst Clin Transfus Med & Immunogenet Ulm, German Red Cross Blood Donat Serv, D-89081 Ulm, Germany. [Zeplin, Philip Helge] Schlosspk Klin Ludwigsburg, Privatklin Plast & Asthet Chirurg, D-71638 Ludwigsburg, Germany. [Funk, Wolfgang] Schonheitsklin Dr Funk, D-81739 Munich, Germany. C3 Ulm University; Ulm University; Ulm University RP Kochanek, S (corresponding author), Univ Med Ctr Ulm, Dept Gene Therapy, D-89081 Ulm, Germany. EM Robin.nilson@uni-ulm.de; olivia.luebbers@hotmail.de; linus.weiss@yahoo.de; karmveer.singh@uni-ulm.de; karin.scharffetter-kochanek@uni-ulm.de; markus.rojewski@uni-ulm.de; h.schrezenmeier@blutspende.de; p.zeplin@schlosspark-klinik.com; info@schoenheitsklinik.com; Lea.krutzke@uni-ulm.de; Stefan.Kochanek@uni-ulm.de; astrid.kritzinger@uni-ulm.de RI ; Singh, Karmveer/ABA-8715-2021 OI Singh, Karmveer/0000-0002-1237-7417; Nilson, Robin/0000-0002-2528-9547; Kochanek, Stefan/0000-0001-7494-1602; Weiss, Linus/0000-0002-6905-5283; Krutzke, Lea/0000-0002-4092-4131 FU German Federal Ministry of Education and Research (BMBF); Federal States of Germany Grant "Innovative Hochschule" [FKZ 3IHS024D]; European Commission [241879, 643809]; Sanitatsakademie der Bundeswehr [E/U2AD/ID018/IF557] FX The work was supported by the German Federal Ministry of Education and Research (BMBF) and the Federal States of Germany Grant "Innovative Hochschule" (FKZ 3IHS024D). Parts of this re-search were funded by the 7th framework programme of the European Commission (project title REBORNE, grant agreement number 241879), the H2020 Programme of the European Commission (project title ADIPOA-2, grant agreement number 643809) and by the Sanitatsakademie der Bundeswehr E/U2AD/ID018/IF557. The materials presented and views expressed here are the responsibility of the authors only. The EU Commission takes no responsibility for any use made of the information set out. 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Challenges in glioma treatment include the difficulty for drugs to cross the blood-brain barrier when administered systemically and poor drug diffusion when administered locally. Mesenchymal stem cells exhibit advantages for glioma therapy because of their ability to pass through the blood-brain barrier and migrate to tumor cells and their tolerance to the immune system. Therefore, mesenchymal stem cells have been explored as vehicles for various therapeutic agents for glioma treatment. Mesenchymal stem cells loaded with chemotherapeutic drugs show improved penetration and tumor accumulation. For gene therapy, mesenchymal stem cells can be used as vehicles for suicide genes, the so-called gene-directed enzyme prodrug therapy. Mesenchymal stem cell-based oncolytic viral therapies have been attempted in recent years to enhance the efficacy of infection against the tumor, viral replication, and distribution of viral particles. Many uncertainties remain regarding the function and behavior of mesenchymal stem cells in gliomas. However, strategies to increase mesenchymal stem cell migration to gliomas may improve the delivery of therapeutic agents and enhance their anti-tumor effects, representing promising potential for patient treatment. C1 [Oishi, Tomoya; Koizumi, Shinichiro; Kurozumi, Kazuhiko] Hamamatsu Univ, Sch Med, Dept Neurosurg, Hamamatsu, Shizuoka, Japan. C3 Hamamatsu University School of Medicine RP Kurozumi, K (corresponding author), Hamamatsu Univ, Sch Med, Dept Neurosurg, Hamamatsu, Shizuoka, Japan. 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PD SEP PY 2024 VL 31 IS 9 BP 1306 EP 1314 DI 10.1038/s41417-024-00775-7 EA APR 2024 PG 9 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA G1D2Z UT WOS:001207027700001 PM 38654128 DA 2025-10-02 ER PT J AU Bovenberg, MSS Degeling, MH Tannous, BA AF Bovenberg, M. Sarah S. Degeling, M. Hannah Tannous, Bakhos A. TI Advances in stem cell therapy against gliomas SO TRENDS IN MOLECULAR MEDICINE LA English DT Review DE neural stem cells; mesenchymal stem cells; hematopoietic stem cells; cell therapy; glioma; clinical trials; gene therapy; prodrug; oncolytic virus ID MESENCHYMAL STROMAL CELLS; GENE-THERAPY; BONE-MARROW; ONCOLYTIC ADENOVIRUS; NEURAL PRECURSORS; BRAIN-TUMORS; DELIVERY; GLIOBLASTOMA; TROPISM; DIFFERENTIATION AB Malignant gliomas are one of the most lethal cancers, and despite extensive research very little progress has been made in improving prognosis. Multimodality treatment combining surgery, radiation, and chemotherapy is the current gold standard, but effective treatment remains difficult due to the invasive nature and high recurrence of gliomas. Stem cell-based therapy using neural, mesenchymal, or hematopoietic stem cells may be an alternative approach because it is tumor selective and allows targeted therapy that spares healthy brain tissue. Stem cells can be used to establish a long-term antitumor response by stimulating the immune system and delivering prodrug, metabolizing genes, or oncolytic viruses. In this review, we discuss current trends and the latest developments in stem cell therapy against malignant gliomas from both the experimental laboratory and the clinic. C1 [Bovenberg, M. Sarah S.; Degeling, M. Hannah; Tannous, Bakhos A.] Massachusetts Gen Hosp, Dept Neurol, Neurosci Ctr, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. [Bovenberg, M. Sarah S.; Degeling, M. Hannah; Tannous, Bakhos A.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Bovenberg, M. Sarah S.; Degeling, M. Hannah] Leiden Univ, Med Ctr, Dept Neurosurg, Leiden, Netherlands. C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC RP Tannous, BA (corresponding author), Massachusetts Gen Hosp, Dept Neurol, Neurosci Ctr, Expt Therapeut & Mol Imaging Lab, Boston, MA 02129 USA. EM btannous@hms.harvard.edu RI Tang, Dingzhong/AAZ-2500-2020 FU National Institutes of Health; National Institute of Neurological Disorders and Stroke [1R01NS064983]; National Cancer Institute [1R01CA166077]; Fulbright scholarship; Saal van Zwanenberg Foundation; VSB fonds; Dr Hendrik Muller Vaderlandschfonds; Dutch Cancer Foundation (KWF Kankerbestrijding); Hersenstichting brain fund; Jo Keur (Leiden hospital) FX B.A.T. is supported by grants from the National Institutes of Health, the National Institute of Neurological Disorders and Stroke (1R01NS064983) and the National Cancer Institute (1R01CA166077). M.H.D. is supported by a Fulbright scholarship, the Saal van Zwanenberg Foundation, VSB fonds, Dr Hendrik Muller Vaderlandschfonds, the Dutch Cancer Foundation (KWF Kankerbestrijding), the Hersenstichting brain fund, as well as the Jo Keur (Leiden hospital). M.S.B. is supported by a Fulbright scholarship, the Huygens Scholarship Program, VSB fonds and the Saal van Zwanenberg Foundation. The authors would like to thank Mr Romain Amante for assistance in drawing Figure 2. 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Med PD MAY PY 2013 VL 19 IS 5 BP 281 EP 291 DI 10.1016/j.molmed.2013.03.001 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 155AH UT WOS:000319717300003 PM 23537753 DA 2025-10-02 ER PT S AU Dittmar, T Entschladen, F AF Dittmar, Thomas Entschladen, Frank BE Weyand, B Dominici, M Hass, R Jacobs, R Kasper, C TI Migratory Properties of Mesenchymal Stem Cells SO MESENCHYMAL STEM CELLS: BASICS AND CLINICAL APPLICATION I SE Advances in Biochemical Engineering-Biotechnology LA English DT Article; Book Chapter DE Mesenchymal stem cells; MSCs; Inflammation; Tumor tropism; Trojan horse ID MARROW STROMAL CELLS; BREAST-CANCER CELLS; BONE-MARROW; TUMOR STROMA; IN-VITRO; CARCINOMA CELLS; ONCOLYTIC ADENOVIRUS; HEMATOPOIETIC STEM; TARGETED-DELIVERY; INTERFERON-BETA AB Mesenchymal stem cells raise great expectations in regenerative medicine due to their capacity to regenerate damaged tissues, thereby restoring organ tissue integrity and functionality. Even though it is not yet clear how mesenchymal stem cells are guided to injured tissue it is generally assumed that the directed migration of these cells is facilitated by the same soluble factors that also recruit immune competent cells to inflamed tissue areas. Tumor tissue represents another type of (chronically) inflamed tissue and because of that mesenchymal stem cells are highly attracted. Although some data indicate that esenchymal stem cells might have a beneficial effect on tumor growth due to anti-tumor effects the plethora of data suggest that tumor tissue recruited mesenchymal stem cells rather promote tumor growth and metastasis formation. Nonetheless, the enhanced tumor tropism of mesenchymal stem cells makes them ideal candidates for novel anti-cancer strategies. Like Trojan Horses genetically modified mesenchymal stem cells will deliver their deadly cargo, such as anti-tumor cytokines or oncolytic viruses, into cancerous tissues, thereby destroying the tumor form within. In this chapter we will summarize the current concepts of genetic modification of mesenchymal stem cells for future anti-cancer therapies. C1 [Dittmar, Thomas; Entschladen, Frank] Univ Witten Herdecke, Ctr Biomed Res & Educ, Inst Immunol, D-58448 Witten, Germany. C3 Witten Herdecke University RP Dittmar, T (corresponding author), Univ Witten Herdecke, Ctr Biomed Res & Educ, Inst Immunol, Stockumer Str 10, D-58448 Witten, Germany. 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SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0724-6145 EI 1616-8542 BN 978-3-642-35671-1; 978-3-642-35670-4 J9 ADV BIOCHEM ENG BIOT JI Adv. Biochem. Eng. Biotechnol. PY 2013 VL 129 BP 117 EP 136 DI 10.1007/10_2012_144 D2 10.1007/978-3-642-35671-1 PG 20 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology WE Book Citation Index – Science (BKCI-S); Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Biotechnology & Applied Microbiology GA BFR89 UT WOS:000321104500008 PM 22899378 DA 2025-10-02 ER PT J AU Gentile, P AF Gentile, Pietro TI Breast Cancer Therapy: The Potential Role of Mesenchymal Stem Cells in Translational Biomedical Research SO BIOMEDICINES LA English DT Review DE breast cancer; breast cancer and mesenchymal stem cells; breast cancer therapy and stem cells; regenerative plastic surgery; plastic surgery ID EXTRACELLULAR VESICLES; STROMAL CELLS; ONCOLYTIC VIROTHERAPY; TARGETED DELIVERY; EXOSOMES; GROWTH; LUNG; METASTASES; DORMANCY; VIRUSES AB The potential role of mesenchymal stem cells (MSCs) in the treatment of metastatic cancers, including breast cancer, has been investigated for many years leading to encouraging results. The role of fat grafting and the related adipose-derived mesenchymal stem cells (AD-MSCs) has been detailed and described for breast reconstruction purposes confirming the safety of AD-MSCs. MSCs have great potential for delivering anticancer agents, suicide genes, and oncolytic viruses to tumors. Currently, many studies have focused on the products of MSCs, including extracellular vesicles (EVs), as a cell-free therapy. This work aimed to review and discuss the current knowledge on MSCs and their EVs in breast cancer therapy. C1 [Gentile, Pietro] Tor Vergata Univ, Dept Surg Sci, I-00133 Rome, Italy. [Gentile, Pietro] Acad Int Regenerat Med & Surg Soc AIRMESS, CH-1201 Geneva, Switzerland. C3 University of Rome Tor Vergata RP Gentile, P (corresponding author), Tor Vergata Univ, Dept Surg Sci, I-00133 Rome, Italy.; Gentile, P (corresponding author), Acad Int Regenerat Med & Surg Soc AIRMESS, CH-1201 Geneva, Switzerland. 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BIOMEDICINES JI Biomedicines PD MAY PY 2022 VL 10 IS 5 AR 1179 DI 10.3390/biomedicines10051179 PG 11 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Pharmacology & Pharmacy GA 1Q2KA UT WOS:000802522000001 PM 35625915 OA Green Published, gold DA 2025-10-02 ER PT J AU Zhang, Q Xiang, W Yi, DY Xue, BZ Wen, WW Abdelmaksoud, A Xiong, NX Jiang, XB Zhao, HY Fu, P AF Zhang, Qing Xiang, Wei Yi, Dong-ye Xue, Bing-zhou Wen, Wan-wan Abdelmaksoud, Ahmed Xiong, Nan-xiang Jiang, Xiao-bing Zhao, Hong-yang Fu, Peng TI Current status and potential challenges of mesenchymal stem cell-based therapy for malignant gliomas SO STEM CELL RESEARCH & THERAPY LA English DT Review DE Mesenchymal stem cells (MSCs); Gliomas; MSC-based therapy; Current status; Potential challenges ID BONE-MARROW; IN-VITRO; UMBILICAL-CORD; STROMAL CELLS; GENE-THERAPY; ONCOLYTIC ADENOVIRUS; INTRACRANIAL GLIOMA; CYTOSINE DEAMINASE; CONDITIONED MEDIUM; PROGENITOR CELLS AB Glioma, which accounts for more than 30% of primary central nervous system tumours, is characterised by symptoms such as headaches, epilepsy, and blurred vision. Glioblastoma multiforme is the most aggressive, malignant, and lethal brain tumour in adults. Even with progressive combination treatment with surgery, radiotherapy, and chemotherapy, the prognosis for glioma patients is still extremely poor. Compared with the poor outcome and slowly developing technologies for surgery and radiotherapy, the application of targeted chemotherapy with a new mechanism has become a research focus in this field. Moreover, targeted therapy is promising for most solid tumours. The tumour-tropic ability of stem cells, including neural stem cells and mesenchymal stem cells, provides an alternative therapeutic approach. Thus, mesenchymal stem cell-based therapy is based on a tumour-selective capacity and has been thought to be an effective anti-tumour option over the past decades. An increasing number of basic studies on mesenchymal stem cell-based therapy for gliomas has yielded complex outcomes. In this review, we summarise the biological characteristics of human mesenchymal stem cells, and the current status and potential challenges of mesenchymal stem cell-based therapy in patients with malignant gliomas. C1 [Zhang, Qing; Xiang, Wei; Yi, Dong-ye; Xue, Bing-zhou; Abdelmaksoud, Ahmed; Xiong, Nan-xiang; Jiang, Xiao-bing; Zhao, Hong-yang; Fu, Peng] Huazhong Univ Sci & Technol, Dept Neurosurg, Union Hosp, Tongji Med Coll, Ave Jiefang 1277, Wuhan 430022, Hubei, Peoples R China. [Wen, Wan-wan] Capital Med Univ, Beijing Anzhen Hosp, Dept Cardiol, 2 Anzhen Rd, Beijing 100029, Peoples R China. C3 Huazhong University of Science & Technology; Capital Medical University RP Fu, P (corresponding author), Huazhong Univ Sci & Technol, Dept Neurosurg, Union Hosp, Tongji Med Coll, Ave Jiefang 1277, Wuhan 430022, Hubei, Peoples R China. EM pfu@hust.edu.cn RI Fu, Peng/D-6010-2017 FU National Natural Science Foundation of China [81572488]; Science and Technology Department of Hubei Province [2015CFB458, 2017CFB268] FX This work was partly supported by a grant from the National Natural Science Foundation of China (no. 81572488) to WX and grants from the Science and Technology Department of Hubei Province (2015CFB458 and 2017CFB268) to PF. 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Ther. PD AUG 24 PY 2018 VL 9 AR 228 DI 10.1186/s13287-018-0977-z PG 9 WC Cell & Tissue Engineering; Cell Biology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Research & Experimental Medicine GA GR4JD UT WOS:000442569700002 PM 30143053 OA gold, Green Published DA 2025-10-02 ER PT J AU Muhammad, T Sakhawat, A Khan, AA Ma, L Gjerset, RA Huang, YH AF Muhammad, Tahir Sakhawat, Ali Khan, Aamir Ali Ma, Ling Gjerset, Ruth A. Huang, Yinghui TI Mesenchymal stem cell-mediated delivery of therapeutic adenoviral vectors to prostate cancer SO STEM CELL RESEARCH & THERAPY LA English DT Article DE Mesenchymal stem cells; Prostate cancer; Adenoviral vectors; Apoptosis; p53 ID GENE-THERAPY; INTRAVITAL MICROSCOPY; SUSCEPTIBILITY LOCI; ANGIOGENESIS; SUPPRESSION; STRATEGIES; LINES; P53 AB BackgroundThere is an urgent need for targeted biological therapies for prostate cancer with greater efficacy and less toxicity, particularly for metastatic disease, where current therapies are not curative. Therapeutic adenoviral vectors or oncolytic adenoviruses offer the possibility of a competent, nontoxic therapeutic alternative for prostate cancer. However, free viral particles must be delivered locally, an approach that does not address metastatic disease, and they display poor tumor penetration. To fully exploit the potential of these vectors, we must develop methods that improve intratumoral dissemination and allow for systemic delivery. This study establishes a proof-of-principle rationale for a novel human mesenchymal stem (stromal) cell-based approach to improving vector delivery to tumors.Methods/resultsWe have generated mesenchymal stem cell-derived packaging cells for adenoviruses (E1-modified mesenchymal stem cells) by modifying human mesenchymal stem cells with the adenovirus (type C) E1A/B genes needed for viral replication. Using cell-based assays, we have demonstrated that two adenoviral vectors, replication-defective adenovirus expressing p14 and p53 or conditionally replicating oncolytic adenovirus, packaged by E1A/B-modified mesenchymal stem cells, suppress the growth of prostate cancer cells in culture. Using subcutaneous xenograft models for human prostate cancer in mice, we have shown that E1A/B-modified mesenchymal stem cells display tumor tropism in tumor-bearing nude mice, that E1A/B-modified mesenchymal stem cells disseminate well within tumors, and that replication-defective adenovirus expressing p14 and p53 or conditionally replicating oncolytic adenovirus-loaded E1-modified mesenchymal stem cells suppresses tumor growth in mice.ConclusionThe results show that this approach, if optimized, could circumvent the obstacles to efficient gene delivery encountered with current gene delivery approaches and provide an effective, nontoxic therapeutic alternative for metastatic disease. C1 [Muhammad, Tahir; Sakhawat, Ali; Khan, Aamir Ali; Ma, Ling; Huang, Yinghui] Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing, Peoples R China. [Gjerset, Ruth A.] Torrey Pines Inst Mol Studies, San Diego, CA USA. C3 Beijing University of Technology; Torrey Pines Institute for Molecular Studies RP Huang, YH (corresponding author), Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing, Peoples R China. EM m.tahir.qau@hotmail.com; huangyh@hotmail.com RI ; huang, ikky/IWM-6280-2023; tahir, muhammad/KAM-3327-2024; Ali, Sakhawat/R-7877-2019; Khan, Dr. Aamir/AAD-5959-2021 OI Ali, Sakhawat/0000-0003-0295-2163; Ali Khan, Dr. Aamir/0000-0003-1193-8806; FU Natural science foundation China [81472209]; Beijing municipal science and technology commission [K2015311201501] FX The design of the study and sample collection were supported by Natural science foundation China (Grant #81472209), the experimental analysis, interpretation of data and manuscript preparation were supported by the key programs of Beijing municipal science and technology commission (Grant# K2015311201501). 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Ther. PD JUN 25 PY 2019 VL 10 AR 190 DI 10.1186/s13287-019-1268-z PG 12 WC Cell & Tissue Engineering; Cell Biology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Research & Experimental Medicine GA IF2WX UT WOS:000472942100004 PM 31238944 OA Green Published, gold DA 2025-10-02 ER PT J AU Cejalvo, T Perisé-Barrios, AJ del Portillo, I Laborda, E Rodriguez-Milla, MA Cubillo, I Vázquez, F Sardón, D Ramirez, M Alemany, R del Castillo, N García-Castro, J AF Cejalvo, Teresa Perise-Barrios, Ana Judith del Portillo, Isabel Laborda, Eduardo Rodriguez-Milla, Miguel A. Cubillo, Isabel Vazquez, Fernando Sardon, David Ramirez, Manuel Alemany, Ramon del Castillo, Noemi Garcia-Castro, Javier TI Remission of Spontaneous Canine Tumors after Systemic Cellular Viroimmunotherapy SO CANCER RESEARCH LA English DT Article ID SOFT-TISSUE SARCOMAS; MESENCHYMAL STEM-CELLS; ONCOLYTIC ADENOVIRUS; CANCER; DOGS; NEUROBLASTOMA; IMMUNOTHERAPY; HYALURONIDASE; VIROTHERAPY; THERAPIES AB Dogs with spontaneous tumors treated in veterinary hospitals offer an excellent opportunity for studying immunotherapies, including oncolytic viruses. Oncolytic viruses have advanced into the clinic as an intratumorally administered therapeutic; however, intravenous delivery has been hindered by neutralization in the blood. To circumvent this hurdle, mesenchymal stem cells have been used as a "Trojan horse." Here, we present the treatment of 27 canine patients with cancer with canine mesenchymal stem cells infected with ICOCAV17, a canine oncolytic adenovirus. No significant adverse effects were found. The response rate was 74%, with 14.8% showing complete responses, including total remissions of lung metastasis. We detected virus infection, stromal degeneration, and immune cell infiltration in tumor biopsies after 4 weeks of treatment. The increased presence of antiadenoviral antibodies in the peripheral blood of treated dogs did not appear to prevent the clinical benefit of this therapy. These data indicate thatoncolytic viruses loaded in mesenchymal stem cells represent an effective cancer immunotherapy. Significance: The classical clinical limitations of antitumoral viroimmunotherapy can be overcome by use of mesenchymal stem cells. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/17/4891/F1.large.jpg. (C) 2018 AACR. C1 [Cejalvo, Teresa; Perise-Barrios, Ana Judith; Rodriguez-Milla, Miguel A.; Cubillo, Isabel; Garcia-Castro, Javier] ISCIII, Unidad Biotecnol Celular, Madrid, Spain. [del Portillo, Isabel; Vazquez, Fernando; Sardon, David; del Castillo, Noemi] Alfonso X Univ, Vet Hosp, Madrid, Spain. [Laborda, Eduardo; Alemany, Ramon] IDIBELL, Inst Catal Oncol, Barcelona, Spain. [Ramirez, Manuel] Hosp Univ Nino Jesus, Serv Oncohematol & Trasplante, Madrid, Spain. C3 Instituto de Salud Carlos III; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); University of Barcelona; Institut Catala d'Oncologia RP García-Castro, J (corresponding author), Avda Majadahonda Pozuelo Km 2, Madrid 28220, Spain. EM jgcastro@isciii.es RI Garcia-Castro, Javier/ABC-9741-2021; Ramirez, Manuel/H-7710-2015; Rodriguez, Miguel/L-7340-2014; Perisé Barrios, Ana Judith/A-4007-2019; Garcia-Castro, Javier/H-5274-2011 OI Ramirez, Manuel/0000-0003-0332-6973; Cejalvo, Teresa/0000-0002-4304-2150; Perise Barrios, Ana Judith/0000-0002-0136-3968; Garcia-Castro, Javier/0000-0001-7604-1640 FU Fondo de Investigaciones Sanitarias [FIS: PI11/00377, PI17CIII/00013, RD12/0036/0027]; Madrid Regional Government (CellCAM) [P2010/BMD-2420]; Asociacion Pablo Ugarte [G86121019] FX We want to thank the staff of Veterinary Hospital, the technical staff from the Anatomo-pathological Department, as well as Carolina Jimenez and Giulia Setti for their participation in our studies. We are grateful to A. Gomez Vitores for useful advice on the pathology studies. J. Garcia-Castro was awarded grants from the Fondo de Investigaciones Sanitarias (FIS: PI11/00377, PI17CIII/00013, RD12/0036/0027), the Madrid Regional Government (CellCAM; P2010/BMD-2420), and the Asociacion Pablo Ugarte (G86121019). The experiments were approved by the appropriate committees. 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PD SEP 1 PY 2018 VL 78 IS 17 BP 4891 EP 4901 DI 10.1158/0008-5472.CAN-17-3754 PG 11 WC Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology GA GS5YL UT WOS:000443753700009 PM 29991502 OA Green Submitted DA 2025-10-02 ER PT J AU Hochheuser, C Kunze, NY Tytgat, GAM Voermans, C Timmerman, I AF Hochheuser, Caroline Kunze, Nina Y. Tytgat, Godelieve A. M. Voermans, Carlijn Timmerman, Ilse TI The Potential of Mesenchymal Stromal Cells in Neuroblastoma Therapy for Delivery of Anti-Cancer Agents and Hematopoietic Recovery SO JOURNAL OF PERSONALIZED MEDICINE LA English DT Review DE neuroblastoma; mesenchymal stem; stromal cells; hematopoietic stem cell transplantation; drug delivery; oncolytic virotherapy; biodistribution; cellular therapy AB Neuroblastoma is one of the most common pediatric cancers and a major cause of cancer-related death in infancy. Conventional therapies including high-dose chemotherapy, stem cell transplantation, and immunotherapy approach a limit in the treatment of high-risk neuroblastoma and prevention of relapse. In the last two decades, research unraveled a potential use of mesenchymal stromal cells in tumor therapy, as tumor-selective delivery vehicles for therapeutic compounds and oncolytic viruses and by means of supporting hematopoietic stem cell transplantation. Based on pre-clinical and clinical advances in neuroblastoma and other malignancies, we assess both the strong potential and the associated risks of using mesenchymal stromal cells in the therapy for neuroblastoma. Furthermore, we examine feasibility and safety aspects and discuss future directions for harnessing the advantageous properties of mesenchymal stromal cells for the advancement of therapy success. C1 [Hochheuser, Caroline; Tytgat, Godelieve A. M.; Timmerman, Ilse] Princess Maxima Ctr Pediat Oncol, NL-3584 CS Utrecht, Netherlands. [Hochheuser, Caroline; Kunze, Nina Y.; Voermans, Carlijn; Timmerman, Ilse] Univ Amsterdam, Amsterdam UMC, Dept Hematopoiesis, Sanquin Res & Landsteiner Lab, NL-1066 CX Amsterdam, Netherlands. C3 Princess Maxima Center; University of Amsterdam RP Timmerman, I (corresponding author), Princess Maxima Ctr Pediat Oncol, NL-3584 CS Utrecht, Netherlands.; Timmerman, I (corresponding author), Univ Amsterdam, Amsterdam UMC, Dept Hematopoiesis, Sanquin Res & Landsteiner Lab, NL-1066 CX Amsterdam, Netherlands. EM c.h.hochheuser@prinsesmaximacentrum.nl; n.kunze@sanquin.nl; g.a.m.tytgat@prinsesmaximacentrum.nl; c.voermans@sanquin.nl; i.timmerman@sanquin.nl RI ; Voermans, Carlijn/GPP-3405-2022; tytgat, g/ABF-6481-2020 OI Hochheuser, Caroline/0000-0002-2672-6980; voermans, carlijn/0000-0002-6345-9746; Tytgat, Lieve/0000-0003-4452-0748; FU KiKa [303]; PPOC grant [19-27]; Landsteiner Foundation for Blood Transfusion Research, LSBR grant [F1101]; PMC grant [P0104] FX This research was funded by KiKa, grant 303, PPOC grant 19-27 (I.T.), the Landsteiner Foundation for Blood Transfusion Research, LSBR grant F1101 (I.T. and C.V.), PMC grant P0104 (G.A.M.T., C.H.). 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Pers. Med. PD MAR PY 2021 VL 11 IS 3 AR 161 DI 10.3390/jpm11030161 PG 23 WC Health Care Sciences & Services; Medicine, General & Internal WE Science Citation Index Expanded (SCI-EXPANDED) SC Health Care Sciences & Services; General & Internal Medicine GA RD9HG UT WOS:000633778700001 PM 33668854 OA Green Submitted, gold DA 2025-10-02 ER PT J AU Wang, XY Zhao, X He, ZX AF Wang, Xianyao Zhao, Xing He, Zhixu TI Mesenchymal stem cell carriers enhance anti-tumor efficacy of oncolytic virotherapy SO ONCOLOGY LETTERS LA English DT Review DE oncolytic virus; mesenchymal stem cells; cellular carriers; tumor tropism; immunosuppressive function; oncolytic virotherapy AB Oncolytic viruses (OVs) specifically infect, replicate and eventually destroy tumor cells, with no concomitant toxicity to adjacent normal cells. Furthermore, OVs can regulate tumor microenvironments and stimulate anti-tumor immune responses. Mesenchymal stem cells (MSCs) have inherent tumor tropisms and immunosuppressive functions. MSCs carrying OVs not only protect viruses from clearing by the immune system, but they also deliver the virus to tumor lesions. Equally, cytokines released by MSCs enhance anti-tumor immune responses, suggesting that MSCs carrying OVs may be considered as a promising strategy in enhancing the anti-tumor efficacies of virotherapy. In the present review, preclinical and clinical studies were evaluated and discussed, as well as the effectiveness of MSCs carrying OVs for tumor treatment. C1 [Wang, Xianyao; Zhao, Xing] Guizhou Med Univ, Ctr Tissue Engn & Stem Cell Res, 9 Beijing Rd, Guiyang 550004, Guizhou, Peoples R China. [Wang, Xianyao; Zhao, Xing; He, Zhixu] Chinese Acad Med Sci, Key Lab Adult Stem Cell Translat Res, 9 Beijing Rd, Guiyang 550004, Guizhou, Peoples R China. [Wang, Xianyao; Zhao, Xing] Guizhou Med Univ, Dept Immunol, Guiyang 550025, Guizhou, Peoples R China. [He, Zhixu] Zunyi Med Univ, Affiliated Hosp, Dept Pediat, Zunyi 563000, Guizhou, Peoples R China. C3 Guizhou Medical University; Chinese Academy of Medical Sciences - Peking Union Medical College; Guizhou Medical University; Zunyi Medical University RP Zhao, X (corresponding author), Guizhou Med Univ, Ctr Tissue Engn & Stem Cell Res, 9 Beijing Rd, Guiyang 550004, Guizhou, Peoples R China.; He, ZX (corresponding author), Chinese Acad Med Sci, Key Lab Adult Stem Cell Translat Res, 9 Beijing Rd, Guiyang 550004, Guizhou, Peoples R China. EM xingzhao@gmc.edu.cn; hzx@gmc.edu.cn RI he, zeying/HCH-3380-2022; Wang, Xianyao/LUY-2454-2024 OI Wang, Xianyao/0000-0002-1742-2045 FU National Natural Science Foundation of China [81871313]; Graduate Student Innovation Program in Guizhou Province [Qian Jiao He YJSCXJH (2020) 143]; Key projects of Guizhou Provincial Department of Science and Technology [Qian Ke He Zhi Cheng (2020) 4Y192]; Guizhou Provincial Natural Science Foundation [(2019)5663]; Program for Top Scientifc and Technological Talents in Guizhou Province [KY (2018)049]; Guizhou Province Science and Technology Talent Platform Project [(2019)5406]; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2018PT31048, 2019PT310013]; Special Grant for Central Government Supporting Local Science and Technology Development, Science and Technology Department of Guizhou Province [(2019)4008] FX This study was supported by the National Natural Science Foundation of China (grant no. 81871313), the Graduate Student Innovation Program in Guizhou Province [grant no. Qian Jiao He YJSCXJH (2020) 143], Key projects of Guizhou Provincial Department of Science and Technology [grant no. Qian Ke He Zhi Cheng (2020) 4Y192], the Guizhou Provincial Natural Science Foundation [grant no. (2019)5663], the Program for Top Scientifc and Technological Talents in Guizhou Province [grant no. KY (2018)049], the Guizhou Province Science and Technology Talent Platform Project [grant no. (2019)5406], the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (grant nos. 2018PT31048 and 2019PT310013) and the Special Grant for Central Government Supporting Local Science and Technology Development, Science and Technology Department of Guizhou Province [grant no. (2019)4008]. 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PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1792-1074 EI 1792-1082 J9 ONCOL LETT JI Oncol. Lett. PD APR PY 2021 VL 21 IS 4 AR 238 DI 10.3892/ol.2021.12499 PG 10 WC Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology GA QI6TG UT WOS:000619109800001 PM 33664802 OA gold, Green Published DA 2025-10-02 ER PT J AU Morales-Molina, A Gambera, S Cejalvo, T Moreno, R Rodríguez-Milla, MA Perisé-Barrios, AJ García-Castro, J AF Morales-Molina, Alvaro Gambera, Stefano Cejalvo, Teresa Moreno, Rafael Angel Rodriguez-Milla, Miguel Judith Perise-Barrios, Ana Garcia-Castro, Javier TI Antitumor virotherapy using syngeneic or allogeneic mesenchymal stem cell carriers induces systemic immune response and intratumoral leukocyte infiltration in mice SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Oncolytic virus; Mesenchymal stem cells; Tumor infiltration; Immune response; Celyvir; Immunotherapy ID NF-KAPPA-B; ONCOLYTIC ADENOVIRUS; CANCER-IMMUNOTHERAPY; BONE-MARROW; IN-VIVO; TUMOR; INFLAMMATION; EXPRESSION; NEUROBLASTOMA; ACTIVATION AB Oncolytic virotherapy uses oncolytic viruses that selectively replicate in cancer cells. The use of cellular vehicles with migration ability to tumors has been considered to increase their delivery to target sites. Following this approach, the antitumor efficacy of the treatment Celyvir (mesenchymal stem cells infected with the oncolytic adenovirus ICOVIR-5) has been demonstrated in patients with neuroblastoma. However, the better efficacy of syngeneic or allogeneic mesenchymal stem cells as cell carriers and the specific role of the immune system in this therapy are still unknown. In this study we use our virotherapy Celyvir with syngeneic and allogeneic mouse mesenchymal stem cells to determine their antitumor efficacy in a C57BL/6 murine adenocarcinoma model. Adoptive transfer of splenocytes from treated mice to new tumor-bearing mice followed by a secondary adoptive transfer to a third group was performed. Similar reduction of tumor growth and systemic activation of the innate and adaptive immune system was observed in groups treated with syngeneic or allogeneic mesenchymal stem cells loaded with ICOVIR-5. Moreover, a different pattern of infiltration was observed by immunofluorescence in Celyvir-treated groups. While non-treated tumors presented higher density of infiltrating immune cells in the periphery of the tumor, both syngeneic and allogeneic Celyvir-treated groups presented higher infiltration of CD45+ cells in the core of the tumor. Therefore, these results suggest that syngeneic and allogeneic Celyvir induce systemic activation of the immune system, similar antitumor effect and a higher intratumoral infiltration of leukocytes. C1 [Morales-Molina, Alvaro; Gambera, Stefano; Cejalvo, Teresa; Angel Rodriguez-Milla, Miguel; Judith Perise-Barrios, Ana; Garcia-Castro, Javier] Inst Salud Carlos III, Cellular Biotechnol Unit, Lab 51-00-031,Ctra Majadahonda Pozuelo Km 2, Madrid 28220, Spain. [Moreno, Rafael] Inst Catalan Oncol IDIBELL, Translat Res Lab, ProCure Program, Virotherapy & Gene Therapy Grp, Barcelona, Spain. C3 Instituto de Salud Carlos III; Institut Catala d'Oncologia; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL) RP García-Castro, J (corresponding author), Inst Salud Carlos III, Cellular Biotechnol Unit, Lab 51-00-031,Ctra Majadahonda Pozuelo Km 2, Madrid 28220, Spain. EM jgcastro@isciii.es RI Gambera, Stefano/X-8631-2019; Garcia-Castro, Javier/ABC-9741-2021; Perisé Barrios, Ana Judith/A-4007-2019; Garcia-Castro, Javier/H-5274-2011; Rodriguez, Miguel/L-7340-2014 OI Cejalvo, Teresa/0000-0002-4304-2150; Perise Barrios, Ana Judith/0000-0002-0136-3968; Gambera, Stefano/0000-0003-2998-8502; Morales-Molina, Alvaro/0000-0003-4532-7667; Garcia-Castro, Javier/0000-0001-7604-1640; Rodriguez, Miguel/0000-0002-2640-5888 FU Ministerio de Economia y Competitividad of Spain [PI14CIII/00005, PI17CIII/00013]; Consejeria de Educacion, Juventud y Deporte of Comunidad de Madrid [P2010/BMD-2420]; Fundacion Oncohematologia Infantil [CIF G83770297]; AFANION [CIF G02223733]; Asociacion Pablo Ugarte [CIF G86121019] FX This study was funded by Ministerio de Economia y Competitividad of Spain (PI14CIII/00005 and PI17CIII/00013 grants to Javier Garcia-Castro); Consejeria de Educacion, Juventud y Deporte of Comunidad de Madrid (P2010/BMD-2420 grant); Fundacion Oncohematologia Infantil (CIF G83770297), AFANION (CIF G02223733), and Asociacion Pablo Ugarte (CIF G86121019), whose support we gratefully acknowledge. 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TI Development of Allogeneic Stem Cell-Based Platform for Delivery and Potentiation of Oncolytic Virotherapy SO CANCERS LA English DT Article DE SNV1; Supernova; CAL1; vaccinia virus; oncolytic virus; cell-based platform; cancer therapy ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MESENCHYMAL STROMAL CELLS; VACCINIA-VIRUS; SMALLPOX VACCINE; INTRATUMORAL IMMUNOTHERAPY; INTERNATIONAL-SOCIETY; THERAPY; ADENOVIRUS; ACAM2000; PHASE-1 AB Simple Summary The therapeutic potential of the oncolytic virotherapy is severely restricted by multiple innate and adaptive immune barriers. Here, we describe how the Supernova (SNV) cell-based oncolytic platform can be utilized to generate off-the-shelf products for cancer treatments. CAL1 vaccinia virus was loaded into adipose-derived mesenchymal stem cells to generate SNV1. SNV1 shows more resistant to rapid inactivation by humoral immune system as compared to naked CAL1 virus leading to a significant and robust improvement of oncolytic virus therapeutic efficacy in multiple animal models. Particularly, SNV1 provided instantly active viral particles for immediate infection and simultaneous release of therapeutic proteins in the injected tumors, potentially improving virus-based cancer therapies in the clinic. We describe the repurposing and optimization of the TK-positive (thymidine kinase) vaccinia virus strain ACAM1000/ACAM2000 (TM) as an oncolytic virus. This virus strain has been widely used as a smallpox vaccine and was also used safely in our recent clinical trial in patients with advanced solid tumors and Acute Myeloid Leukemia (AML). The vaccinia virus was amplified in CV1 cells and named CAL1. CAL1 induced remarkable oncolysis in various human and mouse cancer cells and preferentially amplified in cancer cells, supporting the use of this strain as an oncolytic virus. However, the therapeutic potential of CAL1, as demonstrated with other oncolytic viruses, is severely restricted by the patients' immune system. Thus, to develop a clinically relevant oncolytic virotherapy agent, we generated a new off-the-shelf therapeutic called Supernova1 (SNV1) by loading CAL1 virus into allogeneic adipose-derived mesenchymal stem cells (AD-MSC). Culturing the CAL1-infected stem cells allows the expression of virally encoded proteins and viral amplification prior to cryopreservation. We found that the CAL1 virus loaded into AD-MSC was resistant to humoral inactivation. Importantly, the virus-loaded stem cells (SNV1) released larger number of infectious viral particles and virally encoded proteins, leading to augmented therapeutic efficacy in vitro and in animal tumor models. C1 [Duong Hoang Nguyen; Draganov, Dobrin; Minev, Ivelina; Neuharth, Forrest; Gomez, Alberto; Alamillo, Ashley; Minev, Boris; Santidrian, Antonio F.] Calidi Biotherapeut, San Diego, CA 92037 USA. [Herrmann, Thomas; Haertl, Barbara; Schneider, Laura Edith; Kleinholz, Daniela] StemVac, D-82347 Bernried, Germany. [Minev, Boris] Univ Calif San Diego, Dept Radiat Med & Appl Sci, La Jolla, CA 92093 USA. C3 University of California System; University of California San Diego RP Nguyen, DH; Santidrian, AF (corresponding author), Calidi Biotherapeut, San Diego, CA 92037 USA. 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breast cancer; genetic modification; extracellular vesicle; cancer therapy; cell therapy; cell-free therapy ID VERSUS-HOST-DISEASE; STROMAL CELLS; EXTRACELLULAR VESICLES; ONCOLYTIC VIROTHERAPY; TARGETED DELIVERY; GENE-THERAPY; RISK; RECEPTOR; GROWTH; LUNG AB Breast cancer has a high prevalence among women, with a high mortality rate. The number of people who suffer from breast cancer disease is increasing, whereas metastatic cancers are mostly incurable, and existing therapies have unfavorable side effects. For an extended duration, scientists have dedicated their efforts to exploring the potential of mesenchymal stem cells (MSCs) for the treatment of metastatic cancers, including breast cancer. MSCs could be genetically engineered to boost their anticancer potency. Furthermore, MSCs can transport oncolytic viruses, suicide genes, and anticancer medicines to tumors. Extracellular vesicles (EVs) are MSC products that have attracted scientist's attention as a cell-free treatment. This study narratively reviews the current state of knowledge on engineered MSCs and their EVs as promising treatments for breast cancer. C1 [Fath, Mohsen Karami] Kharazmi Univ, Fac Biol Sci, Dept Cellular & Mol Biol, Tehran, Iran. [Zadian, Seyed Sajjad] Shahid Beheshti Univ Med Sci, Fac Med, Dept Immunol, Tehran, Iran. [Torbati, Samaneh Mohammad Bagherzadeh] Babol Univ Med Sci, Fac Med, Mazandaran, Iran. [Saqagandomabadi, Vahid] Univ Palermo, Dept Biomed Neurosci & Adv Diagnost, Palermo, Italy. [Afshar, Omid Yousefi] Valiasr Hosp, Clin Res Dev Unit, Tabriz, Iran. [Khalilzad, Mohammad] Tabriz Univ Med Sci, Fac Med, Tabriz, Iran. [Abedi, Sara] Univ Tabriz, Fac Nat Sci, Tabriz, Iran. [Moliani, Afshin] Isfahan Univ Med Sci, Isfahan Med Students Res Ctr, Esfahan, Iran. [Barati, Ghasem] Stem Cell Technol Res Ctr, Tehran, Iran. C3 Kharazmi University; Shahid Beheshti University Medical Sciences; Babol University of Medical Sciences; University of Palermo; Tabriz University of Medical Science; University of Tabriz; Isfahan University of Medical Sciences RP Barati, G (corresponding author), Stem Cell Technol Res Ctr, Tehran, Iran. EM m.gh.barati@gmail.com RI nabi afjadi, mohsen/HJA-1747-2022 FX Declared none. 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PY 2025 VL 25 IS 4 BP 431 EP 444 DI 10.2174/0115665240274818231207054037 EA JAN 2024 PG 14 WC Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine GA 2HW4U UT WOS:001293564100001 PM 38275063 DA 2025-10-02 ER PT J AU Di Somma, S Napolitano, F Portella, G Malfitano, AM AF Di Somma, Sarah Napolitano, Fabiana Portella, Giuseppe Malfitano, Anna Maria TI Cross Talk of Macrophages with Tumor Microenvironment Cells and Modulation of Macrophages in Cancer by Virotherapy SO BIOMEDICINES LA English DT Review DE macrophages; tumor microenvironment; cancer; mesenchymal stem cells; fibroblasts; virotherapy ID MESENCHYMAL STEM-CELLS; ONCOLYTIC VIROTHERAPY; BREAST-CANCER; FIBROBLASTS; EXPRESSION; DL922-947; IMMUNITY AB Cellular compartments constituting the tumor microenvironment including immune cells, fibroblasts, endothelial cells, and mesenchymal stromal/stem cells communicate with malignant cells to orchestrate a series of signals that contribute to the evolution of the tumor microenvironment. In this study, we will focus on the interplay in tumor microenvironment between macrophages and mesenchymal stem cells and macrophages and fibroblasts. In particular, cell-cell interaction and mediators secreted by these cells will be examined to explain pro/anti-tumor phenotypes induced in macrophages. Nonetheless, in the context of virotherapy, the response of macrophages as a consequence of treatment with oncolytic viruses will be analyzed regarding their polarization status and their pro/anti-tumor response. C1 [Di Somma, Sarah; Napolitano, Fabiana; Portella, Giuseppe; Malfitano, Anna Maria] Univ Napoli Federico II, Dipartimento Sci Med Traslaz, I-80131 Naples, Italy. C3 University of Naples Federico II RP Portella, G; Malfitano, AM (corresponding author), Univ Napoli Federico II, Dipartimento Sci Med Traslaz, I-80131 Naples, Italy. EM sarah.ds@libero.it; fabiananapolitano94@gmail.com; portella@unina.it; annamaria.malfitano@unina.it RI ; Di Somma, Sarah/HJZ-2437-2023; Portella, Giuseppe/AFU-6826-2022 OI PORTELLA, Giuseppe/0000-0001-8276-9769; Malfitano, Anna Maria/0000-0002-6193-2835; napolitano, fabiana/0000-0002-9242-6046; FU FIRC-AIRC fellowship [24259] FX FundingS.D.S. was supported by FIRC-AIRC fellowship (N.24259). 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Garcia-Castro, Javier TI Mesenchymal stem cell carriers enhance antitumor efficacy of oncolytic adenoviruses in an immunocompetent mouse model SO ONCOTARGET LA English DT Article DE mesenchymal stem cells; carriers; oncolytic adenoviruses; immunotherapy; cancer ID CANCER GENE-THERAPY; EFFECT IN-VIVO; NF-KAPPA-B; TUMOR-MODELS; BONE-MARROW; TOXICITY; ICOVIR-5; IMMUNOTHERAPY; NEUROBLASTOMA; VIROTHERAPY AB Oncolytic virotherapy represents a promising alternative for cancer treatment; however, viral delivery to the tumor represents a major challenge. Mesenchymal stem cells (MSCs) chemotax to tumors, and can serve as a viral delivery tool. Previously, we demonstrated antitumor therapeutic efficacy for mesenchymal stem cells (MSCs) infected with the oncolytic human adenovirus ICOVIR5 (Celyvir) for treatment of neuroblastoma patients. Given the lack of suitable immunocompetent preclinical models, the mechanism underlying Celyvir antitumor activity remains unknown. In this study, we used the syngeneic murine CMT64 cell line as a human adenovirussemi-permissive tumor model and demonstrate the homing capacity of mouse Celyvir (mCelyvir) to CMT64 tumors. We found that the combined treatment of mCelyvir and intratumoral injections (i.t.) of ICOVIR5 was more effective than treatment with i.t. ICOVIR5 alone. Interestingly, the superior therapeutic effect of the combined therapy was associated with a higher tumor infiltration of CD8+ and CD4+ T cells. Our findings suggest that the use of MSCs as carriers of oncolytic adenovirus can improve the clinical efficacy of anti-cancer virotherapy, not only by driving the adenovirus to tumors, but also through their potential to recruit T cells. C1 [Rincon, Esther; Cejalvo, Teresa; Alfranca, Arantzazu; Angel Rodriguez-Milla, Miguel; Garcia-Castro, Javier] Inst Salud Carlos III, Unidad Biotecnol Celular, Madrid, Spain. [Rincon, Esther; Kanojia, Deepak; Han, Yu; Zhang, Lingjiao; Lesniak, Maciej S.] Univ Chicago, Brain Tumor Ctr, Chicago, IL 60637 USA. [Gil Hoyos, Raul Andres; Alemany, Ramon] IDIBELL, Inst Catala Oncol, Barcelona, Spain. C3 Instituto de Salud Carlos III; University of Chicago; University of Barcelona; Institut Catala d'Oncologia; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL) RP García-Castro, J (corresponding author), Inst Salud Carlos III, Unidad Biotecnol Celular, Madrid, Spain. EM jgcastro@isciii.es RI ; zhang, lingjiao/AAC-9015-2019; Yu, Jinghua/L-3794-2017; Rincón, Esther/L-5047-2014; Garcia-Castro, Javier/H-5274-2011; Kanojia, Deepak/G-5120-2014; Alfranca, Arantzazu/E-8804-2018; Garcia-Castro, Javier/ABC-9741-2021 OI Alfranca, Arantzazu/0000-0002-3732-5816; Cejalvo, Teresa/0000-0002-4304-2150; Garcia-Castro, Javier/0000-0001-7604-1640; Kanojia, Deepak/0000-0003-4295-4972; Zhang, Lingjiao/0000-0003-0700-4584; FU Fondo de Investigaciones Sanitarias in Spain [PI05/2217, PI08/0029, PI14CIII/00005]; RTICC in Spain [RD12/0036/0015, RD12/0036/0027]; Madrid Regional Government in Spain [S-BIO-0204-2006, P2010/BMD-2420]; "Sara Borrell" program of the Instituto de Salud Carlos III FX This work was supported by grants from the Fondo de Investigaciones Sanitarias (PI05/2217; PI08/0029; PI14CIII/00005), RTICC (RD12/0036/0015; RD12/0036/0027) and the Madrid Regional Government (S-BIO-0204-2006, MesenCAM; P2010/BMD-2420, CellCAM) in Spain to JG-C. ER and TC are supported by the "Sara Borrell" program of the Instituto de Salud Carlos III. The experiments were approved by the appropriate committees. 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MSC therapy have shown a dual role in cancers, promoting or inhibiting. However, MSCs could be used as a carrier of anticancer agents for targeted tumor therapy. Recent technical improvements also allow engineering MSCs to improve tumor-targeting properties, protect anticancer agents, and decrease the cytotoxicity of drugs. While some of MSC functions are mediated through their secretome, MSCs-derived extracellular vesicles (EVs) are also proposed as a possible viechle for cancer therapy. EVs allow efficient loading of anticancer agents and have an intrinsic ability to target tumor cells, making them suitable for targeted therapy of tumors. In addition, the specificity and selectivity of EVs to the tumor sites could be enhanced by surface modification. In this review, we addressed the current approaches used for engineering MSCs and EVs to effectively target tumor sites and deliver anticancer agents. C1 [Banan, Zahra Moayedi] Kharazmi Univ, Fac Biol Sci, Dept Cellular & Mol Biol, Tehran, Iran. [Banan, Zahra Moayedi] Shahid Beheshti Univ Med Sci, Sch Pharm, Tehran, Iran. [Barati, Reza] Iran Univ Med Sci, Sch Med, Tehran, Iran. [Mohammadrezakhani, Omid] Mazandaran Univ Med Sci, Fac Pharm, Ramsar Campus, Sari, Iran. [Ghaderi, Aliasghar] Univ Tehran Med Sci, Fac Med, Tehran, Iran. [Hatami, Ali] Isfahan Univ Med Sci, Sch Med, Esfahan, Iran. [Ghiabi, Shamim] Islamic Azad Univ, Fac Pharm, Dept Med Chem, Tehran Med Sci, Tehran, Iran. [Zeidi, Nazanin] Long Isl Univ, Div Pharmaceut Sci, Brooklyn, NY USA. [Asgari, Katayoon] Shahid Beheshti Univ Med Sci, Fac Med, Dept Clin Biochem, Tehran, Iran. [Payandeh, Zahra] Karolinska Inst, Dept Med Biochem & Biophys, Div Med Inflammat Res, Stockholm, Sweden. [Barati, Ghasem] Stem Cell Technol Res Ctr, Tehran, Iran. C3 Kharazmi University; Shahid Beheshti University Medical Sciences; Iran University of Medical Sciences; Mazandaran University of Medical Sciences; Tehran University of Medical Sciences; Isfahan University of Medical Sciences; Islamic Azad University; Long Island University; Long Island University-Brooklyn Campus; Shahid Beheshti University Medical Sciences; Karolinska Institutet RP Barati, G (corresponding author), Stem Cell Technol Res Ctr, Tehran, Iran. 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Biophys. Mol. Biol. PD MAR PY 2023 VL 178 BP 1 EP 16 DI 10.1016/j.pbiomolbio.2023.02.001 EA FEB 2023 PG 16 WC Biochemistry & Molecular Biology; Biophysics WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Biophysics GA A2IA2 UT WOS:000953407400001 PM 36781149 DA 2025-10-02 ER PT J AU Draganov, DD Santidrian, AF Minev, I Nguyen, D Kilinc, MO Petrov, I Vyalkova, A Lander, E Berman, M Minev, B Szalay, AA AF Draganov, Dobrin D. Santidrian, Antonio F. Minev, Ivelina Duong Nguyen Kilinc, Mehmet Okyay Petrov, Ivan Vyalkova, Anna Lander, Elliot Berman, Mark Minev, Boris Szalay, Aladar A. TI Delivery of oncolytic vaccinia virus by matched allogeneic stem cells overcomes critical innate and adaptive immune barriers SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article DE Vaccinia; Cancer; Stem Cells; Oncolysis; Oncolytic virus; Virotherapy; Immunity; Immunotherapy ID MESENCHYMAL STROMAL CELLS; NATURAL-KILLER-CELLS; INTERFERON-GAMMA; BONE-MARROW; IFN-GAMMA; INDOLEAMINE 2,3-DIOXYGENASE; LYMPHOCYTE-PROLIFERATION; TUMOR MICROENVIRONMENT; ALLOGRAFT-REJECTION; VASCULAR FRACTION AB BackgroundPrevious studies have identified IFN as an important early barrier to oncolytic viruses including vaccinia. The existing innate and adaptive immune barriers restricting oncolytic virotherapy, however, can be overcome using autologous or allogeneic mesenchymal stem cells as carrier cells with unique immunosuppressive properties.MethodsTo test the ability of mesenchymal stem cells to overcome innate and adaptive immune barriers and to successfully deliver oncolytic vaccinia virus to tumor cells, we performed flow cytometry and virus plaque assay analysis of ex vivo co-cultures of stem cells infected with vaccinia virus in the presence of peripheral blood mononuclear cells from healthy donors. Comparative analysis was performed to establish statistically significant correlations and to evaluate the effect of stem cells on the activity of key immune cell populations.ResultsHere, we demonstrate that adipose-derived stem cells (ADSCs) have the potential to eradicate resistant tumor cells through a combination of potent virus amplification and sensitization of the tumor cells to virus infection. Moreover, the ADSCs demonstrate ability to function as a virus-amplifying Trojan horse in the presence of both autologous and allogeneic human PBMCs, which can be linked to the intrinsic immunosuppressive properties of stem cells and their unique potential to overcome innate and adaptive immune barriers. The clinical application of ready-to-use ex vivo expanded allogeneic stem cell lines, however, appears significantly restricted by patient-specific allogeneic differences associated with the induction of potent anti-stem cell cytotoxic and IFN responses. These allogeneic responses originate from both innate (NK)- and adaptive (T)- immune cells and might compromise therapeutic efficacy through direct elimination of the stem cells or the induction of an anti-viral state, which can block the potential of the Trojan horse to amplify and deliver vaccinia virus to the tumor.ConclusionsOverall, our findings and data indicate the feasibility to establish simple and informative assays that capture critically important patient-specific differences in the immune responses to the virus and stem cells, which allows for proper patient-stem cell matching and enables the effective use of off-the-shelf allogeneic cell-based delivery platforms, thus providing a more practical and commercially viable alternative to the autologous stem cell approach. C1 [Draganov, Dobrin D.; Santidrian, Antonio F.; Minev, Ivelina; Duong Nguyen; Kilinc, Mehmet Okyay; Minev, Boris; Szalay, Aladar A.] Calidi Biotherapeut, San Diego, CA 92121 USA. [Petrov, Ivan; Vyalkova, Anna; Szalay, Aladar A.] Univ Wurzburg, Inst Biochem, Bioctr, D-97070 Wurzburg, Germany. [Minev, Boris; Szalay, Aladar A.] Univ Calif San Diego, Radiat Oncol, Moores Canc Ctr, La Jolla, CA 92037 USA. [Lander, Elliot; Berman, Mark] Calif Stem Cell Treatment Ctr, Rancho Mirage, CA 92270 USA. C3 University of Wurzburg; University of California System; University of California San Diego RP Draganov, DD; Szalay, AA (corresponding author), Calidi Biotherapeut, San Diego, CA 92121 USA.; Szalay, AA (corresponding author), Univ Wurzburg, Inst Biochem, Bioctr, D-97070 Wurzburg, Germany. EM ddraganov@calidibio.com RI ; Draganov, Dobrin/AAF-2518-2020; Nguyen, Duong/HPE-8761-2023 OI Petrov, Ivan/0009-0007-8776-6058; Minev, Boris/0000-0003-0758-7177; FU Calidi Bioterapeutics' - Foundation of the International Cell Surgical Society at Rancho Mirage; Calidi Biotherapeutics FX The authors would like to thank for the PBMC and SVF research sample aliquotes donated by patients at the California Stem Cell Treatment Center. This Calidi Bioterapeutics' funded research was supported by the Foundation of the International Cell Surgical Society at Rancho Mirage, by the cell and tissue imaging facility at the University of Wuerzburg, and by the Stem Cell Facility at StemVac GmbH. We are thankful for the generous research grant support and the donations of graduate student fellowships by the management of Calidi Biotherapeutics. We are thankful to Mr. Stephen Keane and Mrs. Ulrike Szalay for reviewing and editing this manuscript. The authors would also like to express their gratitude to Dennis Young and the Cytometry Core Facility of the Moores Cancer Center, San Diego, CA, for providing technical services in support of this study. 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Transl. Med. PD MAR 27 PY 2019 VL 17 AR 100 DI 10.1186/s12967-019-1829-z PG 22 WC Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine GA HR1VW UT WOS:000462925100002 PM 30917829 OA Green Submitted, gold DA 2025-10-02 ER PT J AU Wang, XY Yang, YC Wang, NX Xu, JW Zhou, YH Wu, XJ He, ZX Zhao, X AF Wang, X-Y Yang, Y-C Wang, N-X Xu, J-W Zhou, Y-H Wu, X-J He, Z-X Zhao, X. TI The influence of oncolytic reovirus on the biological activities of umbilical cord-derived mesenchymal stem cells SO EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES LA English DT Article DE Oncolytic reovirus; Umbilical cord-derived mesenchymal stem cells; Proliferation; Differentiation; Migration ID DELIVERY; VIRUS AB OBJECTIVE: To investigate the influence of oncolytic reovirus on the biological activities of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) as a novel virot herapy strategy. MATERIALS AND METHODS: The Cell Counting Kit-8 assay was used to detect the viability of hUC-MSCs infected with different multiplicities of infection (MOTs) of reoviruses. The biological activities (proliferation, marker expression, multipotency, and migration) of hUC-MSCs were verified by assaying osteogenic and adipogenic differentiation potential, flow cytometry, and electrical cell-substrate impedance sensing, respectively. RESULTS: The viability of hUC-MSCs slightly decreased by infection with low titers of reoviruses. A MOI of 1 had no effect on the viability of hUC-MSCs within 98 h. The biological activities (proliferation, marker expression, multipotency, and migration) of hUC-MSCs were not affected by reovirus infection at a MOI of 1. CONCLUSIONS: Reovirus at a MOI of 1 had no effect on the biol ical activities of hUC-MSCs. C1 [Wang, X-Y; Yang, Y-C; Xu, J-W; Zhou, Y-H; Wu, X-J; Zhao, X.] Guizhou Med Univ, Stem Cell & Tissue Engn Res Ctr, Guiyang, Peoples R China. [Wang, X-Y; Xu, J-W; Zhou, Y-H; Wu, X-J; He, Z-X; Zhao, X.] Chinese Acad Med Sci, Key Lab Adult Stem Cell Translat Res, Guiyang, Peoples R China. [Wang, X-Y; Wang, N-X; Wu, X-J; Zhao, X.] Guizhou Med Univ, Dept Immunol, Guiyang, Peoples R China. [He, Z-X] Zunyi Med Univ, Dept Pediat, Affiliated Hosp, Zunyi, Guizhou, Peoples R China. [Xu, J-W] Guizhou Med Univ, Dept Pharmacol, Guiyang, Peoples R China. C3 Guizhou Medical University; Chinese Academy of Medical Sciences - Peking Union Medical College; Guizhou Medical University; Zunyi Medical University; Guizhou Medical University RP Zhao, X (corresponding author), Guizhou Med Univ, Stem Cell & Tissue Engn Res Ctr, Guiyang, Peoples R China.; He, ZX; Zhao, X (corresponding author), Chinese Acad Med Sci, Key Lab Adult Stem Cell Translat Res, Guiyang, Peoples R China.; Zhao, X (corresponding author), Guizhou Med Univ, Dept Immunol, Guiyang, Peoples R China.; He, ZX (corresponding author), Zunyi Med Univ, Dept Pediat, Affiliated Hosp, Zunyi, Guizhou, Peoples R China. EM hzx@gmc.edu.cn; xingzhao@gmc.edu.cn RI ; Wang, Xianyao/LUY-2454-2024; he, zeying/HCH-3380-2022 OI Wang, Xianyao/0000-0002-1742-2045; FU National Natural Science Foundation of China [81871313, 81860542]; Guizhou Provincial Natural Science Foundation [(2019)5663]; Program for Top Scientific and Technological Talents in Guizhou Province [(2018)049]; Guizhou Province Science and Technology Talent Platform Project [(2019)5406]; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2018PT31048, 2019PT310013] FX This work was supported by the National Natural Science Foundation of China (Grant No. 81871313 and 81860542), the Guizhou Provincial Natural Science Foundation [Grant No. (2019)5663], the Program for Top Scientific and Technological Talents in Guizhou Province [Grant No. KY (2018)049], the Guizhou Province Science and Technology Talent Platform Project [Grant No. (2019)5406], and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (Grant No. 2018PT31048 and 2019PT310013). 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SO ANTICANCER RESEARCH LA English DT Article DE Glioblastoma multiforme; mesenchymal stem cells; varicella zoster virus; virotherapy; malignant glioma; oncolysis; MeWo; MRC5; U87; U251; U373; cell lines ID HERPES-SIMPLEX-VIRUS; MARROW STROMAL CELLS; T-CELL; THERAPY; REPLICATION; ADENOVIRUS; TROPISM; PROTEIN; TRIAL; SKIN AB Background: Glioblastoma multiforme is a highly aggressive tumor with a median survival of 14 months despite all standard therapies. Focusing on alternative treatment strategies, we evaluated the oncolytic potential of varicella zoster virus (VZV) in malignant glioma cell cultures. Materials and Methods: Replication of wildtype and mutant VZV was comparatively analyzed in glioma cell lines (U87, U251 and U373) and in primary malignant glioma cells (n=10) in vitro by infectious foci assay, immunofluorescence microscopy and western blot analysis. Additionally, the tumor-targeting potential of VZV-infected human mesenchymal stem cells was evaluated. Results: VZV. replicated efficiently in all the glioma cells studied here followed by rapid oncolysis in vitro. The attenuated vaccine VZV mutant rOKA/ORF63rev[T171] exhibited most efficient replication. Human mesenchymal stem cells were found suitable for targeting VZV to sites of tumor growth. Conclusion: VZV exhibits an intrinsic oncolytic potential in malignant glioma cell cultures and might be a novel candidate for virotherapy in glioblastoma multiforme. C1 [Leske, Henning; Restle, Florian; Schichor, Christian; Albrecht, Valerie; Tonn, Joerg C.; Thon, Niklas] Hosp Univ Munich, Dept Neurosurg, D-81377 Munich, Germany. [Leske, Henning; Haase, Rudolf; Restle, Florian; Pinto, Maria G. Vizoso; Baiker, Armin] Univ Munich, Max Von Pettenkofer Inst, Dept Virol, Munich, Germany. [Baiker, Armin] Bavarian Hlth & Food Safety Author, Oberschleissheim, Germany. [Leske, Henning] Univ Zurich Hosp, Dept Neuropathol, Zurich, Switzerland. C3 University of Munich; University of Munich; Bavarian Health & Food Safety Authority; University of Zurich; University Zurich Hospital RP Thon, N (corresponding author), Hosp Univ Munich, Dept Neurosurg, Campus Grosshadern,Marchioninistr 15, D-81377 Munich, Germany. EM niklas.thon@med.uni-muenchen.de RI ; Schichor, Christian/D-8635-2014; Tonn, Joerg/AAK-8509-2021; Thon, Niklas/AAI-9069-2021; Vizoso Pinto, Maria Guadalupe/KHV-0500-2024 OI Baiker, Armin/0000-0002-2625-3802; FU bi-national SYSTHER-INREMOS virtual institute; German and Slovenian Federal Ministries of Education and Research; Deutsche Forschungsgemeinschaft [BA 2035/3-1, SFB 824] FX We thank Dr. Ann Arvin (Stanford University, USA) for her generous support and the VZV mutants used in our study. Parts of this work were generously supported by the bi-national SYSTHER-INREMOS virtual institute, funded by the German and Slovenian Federal Ministries of Education and Research and by the Deutsche Forschungsgemeinschaft (BA 2035/3-1 and SFB 824). 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TI Treatment of metastatic neuroblastoma with systemic oncolytic virotherapy delivered by autologous mesenchymal stem cells: an exploratory study SO CANCER GENE THERAPY LA English DT Article DE mesenchymal stem cells; oncolytic adenoviruses; systemic delivery; neuroblastoma; metastases ID BONE-MARROW; CELLULAR VEHICLES; PROGENITOR CELLS; CANCER; TRANSPLANTATION; ADENOVIRUSES; TOXICITY; COTRANSPLANTATION; CHEMOTHERAPY; ICOVIR-5 AB Treatment of metastatic tumors with engineered adenoviruses that replicate selectively in tumor cells is a new therapeutic approach in cancer. Systemic administration of these oncolytic adenoviruses lack metastatic targeting ability. The tumor stroma engrafting property of intravenously injected mesenchymal stem cells (MSCs) may allow the use of MSCs as cellular vehicles for targeted delivery. In this work, we study the safety and the efficacy of infusing autologous MSCs infected with ICOVIR-5, a new oncolytic adenovirus, for treating metastatic neuroblastoma. Four children with metastatic neuroblastoma refractory to front-line therapies received several doses of autologous MSCs carrying ICOVIR-5, under an approved preliminary study. The tolerance to the treatment was excellent. A complete clinical response was documented in one case, and the child is in complete remission 3 years after this therapy. We postulate that MSCs can deliver oncolytic adenoviruses to metastatic tumors with very low systemic toxicity and with beneficial antitumor effects. Cancer Gene Therapy (2010) 17, 476-483; doi:10.1038/cgt.2010.4; published online 19 February 2010 C1 [Garcia-Castro, J.; del Mar Arriero, M.; Lassaletta, A.; Madero, L.; Ramirez, M.] Hosp Univ Nino Jesus, Serv Oncohematol & Trasplante, Madrid 28009, Spain. [Alemany, R.; Cascallo, M.; Martinez-Quintanilla, J.] Inst Catala Oncol, Virus Therapy Grp, Translat Res Lab, Barcelona, Spain. C3 Institut Catala d'Oncologia RP Ramírez, M (corresponding author), Hosp Univ Nino Jesus, Serv Oncohematol & Trasplante, Ave Menendez Pelayo 65, Madrid 28009, Spain. EM mramirezo.hnjs@salud.madrid.org RI Garcia-Castro, Javier/ABC-9741-2021; Martinez-Quintanilla, Jordi/J-9461-2014; Ramirez, Manuel/H-7710-2015; Garcia-Castro, Javier/H-5274-2011; Lassaletta, Alvaro/KPY-5557-2024 OI Martinez-Quintanilla, Jordi/0000-0003-4279-2926; Ramirez, Manuel/0000-0003-0332-6973; LASSALETTA, ALVARO/0000-0003-2881-1473; Garcia-Castro, Javier/0000-0001-7604-1640; FU Instituto de Salud Carlos III [FIS PI05/2217]; Junta de Andalucia [TCRM 0027/2006]; Mutua Madrilena Medical Research Foundation; EU (Theradpox, RA) [18700]; Spanish Ministry of Education and Science [BIO2005-08682-C03-02/01] FX We thank Dr Samuel Navarro for help with electronic microscopy, Dr Jose Diaz for help with MIBG interpretation and Jaime Valentin for technical assistance. Financial support: JG-C supported by Grant FIS PI05/2217 (Instituto de Salud Carlos III) and TCRM 0027/2006 (Junta de Andalucia). MC supported by grant from Mutua Madrilena Medical Research Foundation. RA supported by EU 6th FP research contract 18700 (Theradpox, RA) and project Grant BIO2005-08682-C03-02/01 from the Spanish Ministry of Education and Science. RA belongs to the Network of Cooperative Research on Cancer (C03-10), Instituto de Salud Carlos III of the Ministerio de Sanidad y Consumo, Government of Spain. 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PD JUL PY 2010 VL 17 IS 7 BP 476 EP 483 DI 10.1038/cgt.2010.4 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 611QB UT WOS:000278833800004 PM 20168350 DA 2025-10-02 ER PT J AU Park, JS Kim, M AF Park, Jeong-Soo Kim, Manbok TI Reovirus safety study for proliferation and differentiation of human adipose-derived mesenchymal stem cells SO JOURNAL OF MICROBIOLOGY LA English DT Article DE oncolytic virus; reovirus; safety; human adipose-derived mesenchymal stem cells ID ONCOLYTIC VIRUSES; CANCER; DELIVERY AB Naturally occurring reoviruses are live replication-proficient viruses specifically infecting human cancer cells while sparing the normal counterparts. Stem cells can be highly susceptible to viral infection due to their innate high proliferation potential and other active signaling pathways of cells that might be involved in viral tropism. In the previous study, we showed that reoviruses could adversely affect murine embryonic stem cells' integrity in vitro and in vivo. Oncolytic viruses, delivered systemically face many hurdles that also impede their localization and infection of, metastatic tumors, due to a variety of immune and physical barriers. To overcome such hurdles to systemic delivery, several studies supported the idea that certain types of cells, including mesenchymal stem cells, might play a role as cell carriers for oncolytic viruses. Thus, it would be interesting to examine whether human adult stem cells such as human adipose-derived mesenchymal stem cells could be saved by the reoviral challenge. In this study, we report that biological activities such as proliferation and multi potency of human adipose-derived stem cells are not affected by wild-type reovirus challenge as evidenced by survival, osteogenic and adipogenic differentiation potential assays following treatment with reoviruses. Therefore, unlike murine embryonic stem cells, our study strongly suggests that human adipose-derived adult stem cells could be spared in vivo during wild-type reoviral anti-cancer therapeutics in a clinical setting. Furthermore, the results support the possible clinical use of human adipose-derived stem cells as an effective cell carrier of oncolytic reovirus to maximize their tumor tropism and anti-tumor activity. C1 [Park, Jeong-Soo] Dankook Univ, Coll Med, Dept Biochem, Cheonan 31116, South Korea. [Kim, Manbok] Dankook Univ, Coll Med, Dept Med Sci, Cheonan 31116, South Korea. 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Franco-Luzon, Lidia Ruano, David Gonzalez-Murillo, Africa Alfranca, Arantzazu Casco, Fernando Lassaletta, Alvaro Alonso, Mercedes Madero, Luis Alemany, Ramon Garcia-Castro, Javier Ramirez, Manuel TI Influence of carrier cells on the clinical outcome of children with neuroblastoma treated with high dose of oncolytic adenovirus delivered in mesenchymal stem cells SO CANCER LETTERS LA English DT Article DE Neuroblastoma; Oncolytic virotherapy; Mesenchymal stem cells; Immune response; Cell migration ID STROMAL CELLS; BONE-MARROW; VIRUSES; VIROTHERAPY; MIGRATION; TRIAL; DIFFERENTIATION; PROLIFERATION; CHEMOKINES; VIABILITY AB We report here our clinical experience of a program of compassionate use of Celyvir - autologous marrow derived mesenchymal stem cells (MSCs) carrying an oncolytic adenovirus - for treating children with advanced metastatic neuroblastoma. Children received weekly doses of Celyvir with no concomitant treatments. The tolerance was excellent, with very mild and self-limited viral-related symptoms. Patients could be distinguished based on their response to therapy: those who had a clinical response (either complete, partial or stabilization) and those who did not respond. We found differences between patients who responded versus those who did not when analyzing their respective MSCs, at the expression levels of adhesion molecules (CCR1, CXCR1 and CXCR4) and in migration capacities in transwell assays, and in immune-related molecules (IFN gamma, HLA-DR). These results suggest interpatient differences in the homing and immune modulation capacities of the therapy administered. In addition, the pretherapy immune T cell status and the T effector response were markedly different between responders and non-responders. We conclude that multidoses of Celyvir have an excellent safety profile in children with metastatic neuroblastoma. Intrinsic patients' and MSCs' factors appear to be related to clinical outcome. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Melen, Gustavo J.; Gonzalez-Murillo, Africa] Hosp Univ Nino Jesus, Fdn Invest Biomed, Madrid, Spain. [Melen, Gustavo J.; Ruano, David; Gonzalez-Murillo, Africa; Lassaletta, Alvaro; Madero, Luis; Ramirez, Manuel] Inst Invest Sanitaria La Princesa, Madrid, Spain. [Franco-Luzon, Lidia] Fdn Oncohematol Infantil, Madrid, Spain. [Ruano, David; Lassaletta, Alvaro; Madero, Luis; Ramirez, Manuel] Hosp Univ Nino Jestus, Oncohematol, Madrid, Spain. [Alfranca, Arantzazu; Garcia-Castro, Javier] Inst Salud Carlos III, Unidad Biotecnol Celular, Madrid, Spain. [Casco, Fernando] Hosp Univ Nino Jesus, Anat Patol, Madrid, Spain. [Alonso, Mercedes] Hosp Univ Nino Jesus, Microbiol, Madrid, Spain. [Alemany, Ramon] Inst Catala Oncol IDIBELL, Barcelona, Spain. C3 Instituto de Salud Carlos III; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Institut Catala d'Oncologia RP Ramirez, M (corresponding author), Inst Invest Sanitaria La Princesa, Madrid, Spain.; Ramirez, M (corresponding author), Hosp Univ Nino Jestus, Oncohematol, Madrid, Spain. EM manuel.ramirez@salud.madrid.org RI Franco-Luzón, Lidia/AAO-9792-2020; Lassaletta, Alvaro/KPY-5557-2024; Ramirez, Manuel/H-7710-2015; Gonzalez, Africa/M-3426-2014; Alfranca, Arantzazu/E-8804-2018; Garcia-Castro, Javier/H-5274-2011; Melen, Gustavo/L-5918-2014; Ruano-Gallego, David/ABB-4157-2021; Garcia-Castro, Javier/ABC-9741-2021 OI Ramirez, Manuel/0000-0003-0332-6973; Gonzalez, Africa/0000-0001-7747-1204; LASSALETTA, ALVARO/0000-0003-2881-1473; Franco Luzon, Lidia/0000-0002-7343-8201; Garcia-Castro, Javier/0000-0001-7604-1640; Melen, Gustavo/0000-0001-9743-8903; Alfranca, Arantzazu/0000-0002-3732-5816 FU Fondo de Investigaciones Sanitarias [PI08/0029, PI14CIII/00005, PI13/02487, EC11-061, EC07/90591]; Madrid Regional Government [S-BIO-0204-2006, P2010/BMD-2420]; Asociacion Pablo Ugarte; Asociacion NEN; RTICC [RD12/0036/0027] FX This work was supported by grants from Fondo de Investigaciones Sanitarias PI08/0029 and PI14CIII/00005 to JGC and PI13/02487, EC11-061 and EC07/90591 to MR; RTICC RD12/0036/0027 to JGC; and the Madrid Regional Government (S-BIO-0204-2006, MesenCAM; P2010/BMD-2420, CellCAM) to JGC and MR. MR is supported by Asociacion Pablo Ugarte and by Asociacion NEN. 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PY 2016 VL 371 IS 2 BP 161 EP 170 DI 10.1016/j.canlet.2015.11.036 PG 10 WC Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology GA DE2KX UT WOS:000370457300003 PM 26655276 DA 2025-10-02 ER PT J AU Babaei, A Soleimanjahi, H Soleimani, M Arefian, E AF Babaei, Abouzar Soleimanjahi, Hoorieh Soleimani, Masoud Arefian, Ehsan TI Mesenchymal stem cells loaded with oncolytic reovirus enhances antitumor activity in mice models of colorectal cancer SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Adipose derived-mesenchymal stem cell; Oncolytic virus; Reovirus type 3 dearing; Colorectal cancer ID PHASE-I TRIAL; STROMAL CELLS; VIRUS; THERAPY; DIFFERENTIATION; REPLICATION; MIGRATION; CARRIERS; VITRO AB Oncolytic viruses (OVs) are promising alternative biological agents for treating cancer. However, triggered immune responses against viruses and their delivery to tumor sites are their primary limitations in cancer therapy. To address these challenges, mesenchymal stem cells (MSCs) can serve as permissive tools for OVs loading and delivery to tumor sites. Here, we evaluated the in vitro and in vivo antitumor capability of adiposederived mesenchymal stem cells (AD-MSCs) as a new vehicle for Dearing strain of reovirus (ReoT3D) loading. We first isolated and confirmed the purity of MSCs, and the optimized dose of ReoT3D for MSCs loading was computed by a standard assay. Next, we used murine CT26 cell line to establish the colorectal cancer model in BALB/c mice and demonstrated the antitumor effects of MSCs loaded with reovirus. Our results demonstrated that multiplicity of infection (MOI) 1 pfu/cells of reovirus was the safe dose for loading into purified MSCs. Moreover, our anticancer experiments exhibited that treatment with MSCs loaded with ReoT3D was more effective than ReoT3D and MSCs alone. Higher anticancer impact of MSCs loaded with OV was associated with induction of apoptosis, cell cycle arrests, P53 expression in tumor sections, and reduced tumor growth and size. The present results suggest that MSCs as a permissive shuttle for oncolytic virus (OV) delivery increased the anticancer activity of ReoT3D in mice models of colorectal cancer and these findings should be supported by more preclinical and clinical studies. C1 [Babaei, Abouzar; Soleimanjahi, Hoorieh] Tarbiat Modares Univ, Fac Med Sci, Dept Virol, Tehran, Iran. [Soleimani, Masoud] Tarbiat Modares Univ, Dept Hematol & Cell Therapy, Tehran, Iran. [Soleimani, Masoud] Shahid Beheshti Univ Med Sci, Nano Med & Tissue Engn Res Ctr, Tehran, Iran. [Arefian, Ehsan] Univ Tehran, Coll Sci, Sch Biol, Dept Microbiol, Tehran, Iran. C3 Tarbiat Modares University; Tarbiat Modares University; Shahid Beheshti University Medical Sciences; University of Tehran RP Soleimanjahi, H (corresponding author), Tarbiat Modares Univ, Fac Med Sci, Dept Virol, Tehran, Iran. EM soleim_h@modares.ac.ir RI Arfiane, Ehsan/N-3912-2017; Soleimanjahi, Hoorieh/Y-7846-2019; Soleimanjahi, Hoorieh/B-8945-2017 OI Soleimanjahi, Hoorieh/0000-0003-1931-7801; Arefian, Ehsan/0000-0002-0758-4710 FU Tarbiat Modares University, Faculty of Medical Sciences [Med76015]; National Institute for Medical Research Development (NIMAD) [957970] FX This work was funded by Tarbiat Modares University, Faculty of Medical Sciences (grant number: Med76015) and partially funded by National Institute for Medical Research Development (NIMAD) (grant number: 957970) . 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Pharmacol. PD AUG PY 2021 VL 190 AR 114644 DI 10.1016/j.bcp.2021.114644 EA JUN 2021 PG 11 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA TQ1VI UT WOS:000678074600001 PM 34090878 DA 2025-10-02 ER PT J AU Darestani, NG Gilmanova, AI Al-Gazally, ME Zekiy, AO Ansari, MJ Zabibah, RS Jawad, MA Al-Shalah, SAJ Rizaev, JA Alnassar, YS Mohammed, NM Mustafa, YF Darvishi, M Akhavan-Sigari, R AF Darestani, Nadia Ghasemi Gilmanova, Anna I. Al-Gazally, Moaed E. Zekiy, Angelina O. Ansari, Mohammad Javed Zabibah, Rahman S. Jawad, Mohammed Abed Al-Shalah, Saif A. J. Rizaev, Jasur Alimdjanovich Alnassar, Yasir S. Mohammed, Naseer Mihdi Mustafa, Yasser Fakri Darvishi, Mohammad Akhavan-Sigari, Reza TI Mesenchymal stem cell-released oncolytic virus: an innovative strategy for cancer treatment SO CELL COMMUNICATION AND SIGNALING LA English DT Review DE Oncolytic virus; Mesenchymal stem cell; Cancer treatment; Oncolytic virotherapy; Cellular carriers ID HERPES-SIMPLEX-VIRUS; MEASLES-VIRUS; STROMAL CELLS; BREAST-CANCER; DENDRITIC CELLS; CLINICAL-TRIAL; IN-VITRO; TARGETED DELIVERY; IMMUNE-RESPONSES; VACCINIA VIRUS AB Oncolytic viruses (OVs) infect, multiply, and finally remove tumor cells selectively, causing no damage to normal cells in the process. Because of their specific features, such as, the ability to induce immunogenic cell death and to contain curative transgenes in their genomes, OVs have attracted attention as candidates to be utilized in cooperation with immunotherapies for cancer treatment. This treatment takes advantage of most tumor cells' inherent tendency to be infected by certain OVs and both innate and adaptive immune responses are elicited by OV infection and oncolysis. OVs can also modulate tumor microenvironment and boost anti-tumor immune responses. Mesenchymal stem cells (MSC) are gathering interest as promising anti-cancer treatments with the ability to address a wide range of cancers. MSCs exhibit tumor-trophic migration characteristics, allowing them to be used as delivery vehicles for successful, targeted treatment of isolated tumors and metastatic malignancies. Preclinical and clinical research were reviewed in this study to discuss using MSC-released OVs as a novel method for the treatment of cancer. C1 [Darestani, Nadia Ghasemi] Isfahan Univ Med Sci, Esfahan, Iran. [Al-Gazally, Moaed E.] Univ Al Ameed, Coll Med, Karbala, Iraq. [Gilmanova, Anna I.; Zekiy, Angelina O.] Sechenov Univ, Sechenov First Moscow State Med Univ, Dept Prosthet Dent IM, Moscow, Russia. [Ansari, Mohammad Javed] Prince Sattam Bin Abdulaziz Univ, Coll Pharm, Dept Pharmaceut, Al Kharj, Saudi Arabia. [Zabibah, Rahman S.] Islamic Univ, Coll Med Technol, Med Lab Technol Dept, Najaf, Iraq. [Jawad, Mohammed Abed] Al Nisour Univ Coll, Baghdad, Iraq. [Al-Shalah, Saif A. J.] Al Mustaqbal Univ Coll, Med Labs Tech Dept, Babylon, Iraq. [Rizaev, Jasur Alimdjanovich] Samarkand State Med Univ, Dept Publ Hlth & Healthcare Management, Rector, Samarkand, Uzbekistan. [Alnassar, Yasir S.] Univ Mashreq, Baghdad, Iraq. [Mohammed, Naseer Mihdi] Mazaya Univ Coll, Dept Pharm, Nasiriyah, Dhi Qar, Iraq. [Mustafa, Yasser Fakri] Univ Mosul, Coll Pharm, Dept Pharmaceut Chem, Mosul, Iraq. [Darvishi, Mohammad] AJA Univ Med Sci, Infect Dis & Trop Med Res Ctr IDTMRC, Dept Aerosp & Subaquat Med, Tehran, Iran. [Akhavan-Sigari, Reza] Univ Med Ctr, Dept Neurosurg, Tubingen, Germany. [Akhavan-Sigari, Reza] Warsaw Management Univ, Dept Hlth Care Management & Clin Res, Coll Humanum, Warsaw, Poland. C3 Isfahan University of Medical Sciences; University of Al-Ameed; Sechenov First Moscow State Medical University; Prince Sattam Bin Abdulaziz University; Islamic University College; Al-Nisour University College; Al-Mustaqbal University College; Samarkand State Medical University; Al-Mashreq University; Mazaya University College; University of Mosul; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital RP Darvishi, M (corresponding author), AJA Univ Med Sci, Infect Dis & Trop Med Res Ctr IDTMRC, Dept Aerosp & Subaquat Med, Tehran, Iran. 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Signal. PD FEB 24 PY 2023 VL 21 IS 1 AR 43 DI 10.1186/s12964-022-01012-0 PG 20 WC Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology GA 9J3ZT UT WOS:000940129800002 PM 36829187 OA Green Published, gold DA 2025-10-02 ER PT J AU Petrov, I Gentschev, I Vyalkova, A Elashry, MI Klymiuk, MC Arnhold, S Szalay, AA AF Petrov, Ivan Gentschev, Ivaylo Vyalkova, Anna Elashry, Mohamed I. Klymiuk, Michele C. Arnhold, Stefan Szalay, Aladar A. TI Canine Adipose-Derived Mesenchymal Stem Cells (cAdMSCs) as a "Trojan Horse" in Vaccinia Virus Mediated Oncolytic Therapy against Canine Soft Tissue Sarcomas SO VIRUSES-BASEL LA English DT Article DE oncolytic virus; cancer; vaccinia virus; canine cancer cell lines; canine adipose-derived mesenchymal stem cells (cAdMSCs); canine soft tissue sarcoma (CSTS); canine cancer therapy ID DELIVERY; VIROTHERAPY; DIFFERENTIATION AB Several oncolytic viruses (OVs) including various human and canine adenoviruses, canine distemper virus, herpes-simplex virus, reovirus, and members of the poxvirus family, such as vaccinia virus and myxoma virus, have been successfully tested for canine cancer therapy in preclinical and clinical settings. The success of the cancer virotherapy is dependent on the ability of oncolytic viruses to overcome the attacks of the host immune system, to preferentially infect and lyse cancer cells, and to initiate tumor-specific immunity. To date, several different strategies have been developed to overcome the antiviral host defense barriers. In our study, we used canine adipose-derived mesenchymal stem cells (cAdMSCs) as a "Trojan horse" for the delivery of oncolytic vaccinia virus Copenhagen strain to achieve maximum oncolysis against canine soft tissue sarcoma (CSTS) tumors. A single systemic administration of vaccinia virus-loaded cAdMSCs was found to be safe and led to the significant reduction and substantial inhibition of tumor growth in a CSTS xenograft mouse model. This is the first example that vaccinia virus-loaded cAdMSCs could serve as a therapeutic agent against CSTS tumors. C1 [Petrov, Ivan; Gentschev, Ivaylo; Vyalkova, Anna; Szalay, Aladar A.] Univ Wurzburg, Dept Biochem, Theodor Boveri Inst, Canc Therapy Res Ct, D-97074 Wurzburg, Germany. [Elashry, Mohamed I.; Klymiuk, Michele C.; Arnhold, Stefan] Justus Liebig Univ Giessen, Inst Vet Anat Histol & Embryol, Fac Vet Med, D-35392 Giessen, Germany. [Szalay, Aladar A.] Univ Calif San Diego, Dept Radiat Oncol, Rebecca & John Moores Comprehens Canc Ctr, La Jolla, CA 92093 USA. C3 University of Wurzburg; Justus Liebig University Giessen; University of California System; University of California San Diego RP Petrov, I; Gentschev, I; Szalay, AA (corresponding author), Univ Wurzburg, Dept Biochem, Theodor Boveri Inst, Canc Therapy Res Ct, D-97074 Wurzburg, Germany.; Arnhold, S (corresponding author), Justus Liebig Univ Giessen, Inst Vet Anat Histol & Embryol, Fac Vet Med, D-35392 Giessen, Germany.; Szalay, AA (corresponding author), Univ Calif San Diego, Dept Radiat Oncol, Rebecca & John Moores Comprehens Canc Ctr, La Jolla, CA 92093 USA. EM ivan.petrov@uni-wuerzburg.de; ivaylo.gentschev@mail.uni-wuerzburg.de; anna.vyalkova@uni-wuerzburg.de; Mohammed.Elashry@vetmed.uni-giessen.de; Michele.Klymiuk@vetmed.uni-giessen.de; stefan.arnhold@vetmed.uni-giessen.de; a.szalay_ctrc@uni-wuerzburg.de RI Gentschev, Ivaylo/F-9454-2011; Gentschev, Ivaylo/AAJ-5819-2021; Klymiuk, Michele/A-4676-2010 OI Gentschev, Ivaylo/0000-0003-3743-6329; Petrov, Ivan/0009-0007-8776-6058; Arnhold, Stefan/0000-0001-9455-2727; Elashry, MOHAMED I./0000-0002-6312-2182; Klymiuk, Michele Christian/0000-0002-8934-5114 FU Hope Realized Medical Foundation, (USA); DFG [Fi 573 7-2, 18-1]; Education, Audiovisual and Culture Agency of the European Commission; University of Wuerzburg FX This research was funded by the Hope Realized Medical Foundation, (USA). A.A.S was partially supported by DFG (Fi 573 7-2 and 18-1). Furthermore, it was partially funded by the Education, Audiovisual and Culture Agency of the European Commission in the framework of the Erasmus Mundus Master program EUCOMOR to S.A. The APC was funded by University of Wuerzburg Open Access Publishing funding program. 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Rojas, L. A. Vilardell Villellas, Felip Cervera Soriano, Vanessa Garcia-Castro, J. Fajardo, C. A. Alemany, R. TI Human Menstrual Blood-Derived Mesenchymal Stem Cells as Potential Cell Carriers for Oncolytic Adenovirus SO STEM CELLS INTERNATIONAL LA English DT Article ID STROMAL CELLS; IN-VIVO; DELIVERY; LUNG; NEUROBLASTOMA; MIGRATION; CAPACITY; SUPPRESS; VEHICLES AB Antitumor efficacy of systemically administered oncolytic adenoviruses (OAdv) is limited due to diverse factors such as liver sequestration, neutralizing interactions in blood, elimination by the immune system, and physical barriers in tumors. It is therefore of clinical relevance to improve OAdv bioavailability and tumor delivery. Among the variety of tumor-targeting strategies, the use of stem cells and specifically bone marrow-derived mesenchymal stem cells (BM-MSCs) is of particular interest due to their tumor tropism and immunomodulatory properties. Nonetheless, the invasive methods to obtain these cells, the low number of MSCs present in the bone marrow, and their restricted in vitro expansion represent major obstacles for their use in cancer treatments, pointing out the necessity to identify an alternative source of MSCs. Here, we have evaluated the use of menstrual blood-derived mesenchymal stem cells (MenSCs) as cell carriers for regional delivery of an OAdv in the tumor. Our results indicate that MenSCs can be isolated without invasive methods, they have an increased proliferation rate compared to BM-MSCs, and they can be efficiently infected with different serotype 5-based capsid-modified adenoviruses, leading to viral replication and release. In addition, our in vivo studies confirmed the tumor-homing properties of MenSCs after regional administration. C1 [Moreno, R.; Rojas, L. A.; Fajardo, C. A.; Alemany, R.] Inst Catalan Oncol IDIBELL, Virotherapy & Gene Therapy Grp, ProCure Program, Translat Res Lab, Barcelona, Spain. [Vilardell Villellas, Felip] Hosp Arnau Vilanova, Serv Anat Patol, Lleida, Spain. [Vilardell Villellas, Felip] Inst Recerca Biomed Lleida, Lleida, Spain. [Cervera Soriano, Vanessa] Bellvitge Biomed Res Inst IDIBELL, Genom & Cytom Unit, Barcelona, Spain. [Garcia-Castro, J.] Inst Hlth Carlos III ISCIII, Cellular Biotechnol Lab, Madrid, Spain. C3 Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Institut Catala d'Oncologia; University Hospital Arnau de Vilanova; Institut de Recerca Biomedica - IRB Lleida; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL) RP Moreno, R (corresponding author), Inst Catalan Oncol IDIBELL, Virotherapy & Gene Therapy Grp, ProCure Program, Translat Res Lab, Barcelona, Spain. EM rafamoreno@iconcologia.net RI Villellas, Felip/B-8141-2015; Garcia-Castro, Javier/ABC-9741-2021; Vilardell, Felip/B-8141-2015; Rojas, Luis/ABI-2084-2020; Garcia-Castro, Javier/H-5274-2011 OI Rojas, Luis A./0000-0001-9218-4086; Vilardell, Felip/0000-0002-0876-5425; Garcia-Castro, Javier/0000-0001-7604-1640; Fajardo, Carlos Alberto/0000-0003-4635-2645 FU Asociacion Espanola Contra el Cancer (AECC); Ministerio de Economia y Competitividad of Spain [BIO2014-57716-C2-1-R, PI14CIII/00005, Adenonet BIO2015-68990REDT]; Ris3CAT [COMRDI15-1-0013]; Generalitat de Catalunya [2014SGR364]; European Regional Development Fund FX This work was supported by Asociacion Espanola Contra el Cancer (AECC), BIO2014-57716-C2-1-R grant and PI14CIII/00005 to J G-C from the Ministerio de Economia y Competitividad of Spain, Adenonet BIO2015-68990REDT from the Ministerio de Economia y Competitividad of Spain, Red ADVANCE (CAT) Project COMRDI15-1-0013 from Ris3CAT, and 2014SGR364 research grant from the "Generalitat de Catalunya," cofunded by the European Regional Development Fund, a way to Build Europe. 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PY 2017 VL 2017 AR 3615729 DI 10.1155/2017/3615729 PG 10 WC Cell & Tissue Engineering WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology GA FA4SS UT WOS:000405434100001 PM 28781596 OA Green Submitted, Green Published, gold DA 2025-10-02 ER PT J AU Barlabe, P de Sostoa, J Fajardo, CA Alemany, R Moreno, R AF Barlabe, Paula de Sostoa, Jana Fajardo, Carlos Alberto Alemany, Ramon Moreno, Rafael TI Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers SO CANCER GENE THERAPY LA English DT Article AB Poor tumor targeting of oncolytic adenoviruses (OAdv) after systemic administration is considered a major limitation for virotherapy of disseminated cancers. The benefit of using mesenchymal stem cells as cell carriers for OAdv tumor targeting is currently evaluated not only in preclinical models but also in clinical trials. In this context, we have previously demonstrated the enhanced antitumor efficacy of OAdv-loaded menstrual blood-derived mesenchymal stem cells (MenSCs). However, although significant, the antitumor efficacy obtained was modest, and we hypothesized that a greater antitumor efficacy could be obtained arming the OAdv with a therapeutic transgene. Here we show that combining MenSCs with ICOVIR15-cBiTE, an OAdv expressing an epidermal growth factor receptor (EGFR)-targeting bispecific T-cell engager (cBiTE), enhances the antitumor efficacy compared to MenSCs loaded with the unarmed virus ICOVIR15. We found that MenSCs properly produce cBiTE after viral infection leading to a greater antitumor potency both in vitro and in vivo. These findings indicate the mutual benefit of combining MenSCs and armed OAdv and support the combination of ICOVIR15-cBiTE and MenSCs as a cancer treatment. C1 [Barlabe, Paula; de Sostoa, Jana; Fajardo, Carlos Alberto; Alemany, Ramon; Moreno, Rafael] IDIBELL Inst Catalan Oncol, Oncobell & ProCure Programs, Virotherapy & Gene Therapy Grp, Barcelona, Spain. RP Moreno, R (corresponding author), IDIBELL Inst Catalan Oncol, Oncobell & ProCure Programs, Virotherapy & Gene Therapy Grp, Barcelona, Spain. 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PD MAY PY 2020 VL 27 IS 5 BP 383 EP 388 DI 10.1038/s41417-019-0110-1 PG 6 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA LP4GE UT WOS:000534275700013 PM 31204390 DA 2025-10-02 ER PT J AU Carceller, F Aleu, A Casasco, A Guimaraens, L López-Pino, MA Madero, L Ramírez, M AF Carceller, Fernando Aleu, Aitziber Casasco, Alfredo Guimaraens, Leopoldo Lopez-Pino, Migel A. Madero, Luis Ramirez, Manuel TI Superselective Intracerebral Catheterization for Administration of Oncolytic Virotherapy in a Case of Diffuse Intrinsic Pontine Glioma SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE diffuse intrinsic pontine glioma; virotherapy; angiography ID BRAIN-STEM TUMORS; BCNU AB New therapies are needed to improve current results in diffuse intrinsic pontine glioma. We present here the initial experience of administering Celyvir, autologous mesenchymal stem cells infected with ICOVIR-5, an oncolytic adenovirus that selectively replicates in cancer cells, by means of superselective intra-arterial delivery, in a patient diagnosed of diffuse intrinsic pontine glioma. Feasibility, safety, and morbidity rates of the superselective catheterization technique are comparable with those of diagnostic angiography. The intra-arterial approach warrants a greater contact of the mesenchymal stem cells with the tumor mass, and minimizes hemorrhages or vascular disruption. The tolerance to the 2 administrations was excellent, with no acute or delayed adverse effect, underscoring the feasibility of this technique for the delivery of virotherapies and/or cellular therapies in this location. C1 [Carceller, Fernando; Madero, Luis; Ramirez, Manuel] Hosp Univ Nino Jesus, Dept Oncohematol, Madrid 28009, Spain. [Lopez-Pino, Migel A.] Hosp Univ Nino Jesus, Dept Radiol, Madrid 28009, Spain. [Aleu, Aitziber; Casasco, Alfredo; Guimaraens, Leopoldo] Clin Nuestra Senora del Rosario, Dept Endovasc Therapies, Madrid, Spain. RP Ramírez, M (corresponding author), Hosp Univ Nino Jesus, Serv Oncohematol, Menendez Pelayo 65, Madrid 28009, Spain. 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PD OCT PY 2014 VL 36 IS 7 BP E430 EP E432 DI 10.1097/MPH.0000000000000084 PG 3 WC Oncology; Hematology; Pediatrics WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Hematology; Pediatrics GA AQ8BF UT WOS:000343045300007 DA 2025-10-02 ER PT J AU Ali, S Xia, Q Muhammad, T Liu, LQ Meng, XY Bars-Cortina, D Khan, AA Huang, YH Dong, L AF Ali, Sakhawat Xia, Qin Muhammad, Tahir Liu, Liqun Meng, Xinyi Bars-Cortina, David Khan, Aamir Ali Huang, Yinghui Dong, Lei TI Glioblastoma Therapy: Rationale for a Mesenchymal Stem Cell-based Vehicle to Carry Recombinant Viruses SO STEM CELL REVIEWS AND REPORTS LA English DT Review DE Tumor suppressors; Oncolytic viruses; Mesenchymal stem cells; Targeted delivery ID GENE-THERAPY; ONCOLYTIC VIROTHERAPY; STROMAL CELLS; BONE-MARROW; SUICIDE GENE; IN-VITRO; GLIOMA-CELLS; CANCER CELLS; TUMOR STROMA; P53 PATHWAY AB Evasion of growth suppression is among the prominent hallmarks of cancer. Phosphatase and tensin homolog (PTEN) and p53 tumor-suppressive pathways are compromised in most human cancers, including glioblastoma (GB). Hence, these signaling pathways are an ideal point of focus for novel cancer therapeutics. Recombinant viruses can selectivity kill cancer cells and carry therapeutic genes to tumors. Specifically, oncolytic viruses (OV) have been successfully employed for gene delivery in GB animal models and showed potential to neutralize immunosuppression at the tumor site. However, the associated systemic immunogenicity, inefficient transduction of GB cells, and inadequate distribution to metastatic tumors have been the major bottlenecks in clinical studies. Mesenchymal stem cells (MSCs), with tumor-tropic properties and immune privilege, can improve OVs targeting. Remarkably, combining the two approaches can address their individual issues. Herein, we summarize findings to advocate the reactivation of tumor suppressors p53 and PTEN in GB treatment and use MSCs as a "Trojan horse" to carry oncolytic viral cargo to disseminated tumor beds. The integration of MSCs and OVs can emerge as the new paradigm in cancer treatment. C1 [Ali, Sakhawat; Xia, Qin; Liu, Liqun; Meng, Xinyi; Dong, Lei] Beijing Inst Technol, Sch Life Sci, Beijing 100811, Peoples R China. [Muhammad, Tahir; Khan, Aamir Ali; Huang, Yinghui] Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing 100022, Peoples R China. [Bars-Cortina, David] Paris Saclay Univ, INRAE, Anim Genet & Integrat Biol Dept, F-78350 Paris, France. C3 Beijing Institute of Technology; Beijing University of Technology; INRAE; Universite Paris Saclay RP Dong, L (corresponding author), Beijing Inst Technol, Sch Life Sci, Beijing 100811, Peoples R China. EM ldong@bit.edu.cn RI huang, ikky/IWM-6280-2023; Khan, Dr. Aamir/AAD-5959-2021; tahir, muhammad/KAM-3327-2024; Ali, Sakhawat/R-7877-2019; Liu, Liqun/HRE-2145-2023 OI Ali, Sakhawat/0000-0003-0295-2163; Ali Khan, Dr. Aamir/0000-0003-1193-8806; FU Beijing Natural Science Foundation [Z190018]; National Natural Science Foundation of China [81870123]; National Science Foundation for Young Scientists of China [81902545]; China Postdoctoral Science Foundation [2018M641206] FX The authors gratefully acknowledge the support from the Beijing Natural Science Foundation (Z190018), the National Natural Science Foundation of China (81870123), National Science Foundation for Young Scientists of China (81902545), and China Postdoctoral Science Foundation Grant (2018M641206). 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PD FEB PY 2022 VL 18 IS 2 SI SI BP 523 EP 543 DI 10.1007/s12015-021-10207-w EA JUL 2021 PG 21 WC Cell & Tissue Engineering; Cell Biology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Research & Experimental Medicine GA ZV2OO UT WOS:000678440900002 PM 34319509 DA 2025-10-02 ER PT J AU Zhang, JH Chen, H Chen, C Liu, HM He, YR Zhao, JL Yang, PY Mao, QW Xia, HB AF Zhang, Junhe Chen, Hao Chen, Chen Liu, Haimeng He, Yurou Zhao, Junli Yang, Peiyan Mao, Qinwen Xia, Haibin TI Systemic administration of mesenchymal stem cells loaded with a novel oncolytic adenovirus carrying IL-24/endostatin enhances glioma therapy SO CANCER LETTERS LA English DT Article DE Endostatin; IL-24; MSC; Conditionally replicating adenovirus; Tet-on system ID SUICIDE GENE-THERAPY; ANTITUMOR-ACTIVITY; VIRUS THERAPY; RADIOTHERAPY; VIROTHERAPY; EXPRESSION; EFFICACY; TRAIL AB Oncolytic adenovirus-mediated gene therapy shows promise for cancer treatment; however, the systemic delivery of oncolytic adenovirus to tumors remains challenging. Recently, mesenchymal stem cells (MSCs) have emerged as potential vehicles for improving delivery. Yet, because the oncolytic adenovirus replicates in MSCs, balancing MSC viability with viral load is key to achieving optimal therapeutic effect. We thus developed an allin-one Tet-on system that can regulate replication of oncolytic adenovirus. Then, we loaded the novel oncolytic adenovirus carrying interleukin (IL)-24 and/or Endostatin in human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) for glioma therapy. In vitro assays demonstrated that this novel oncolytic adenovirus could efficiently replicate and kill glioma cells while sparing normal cells. Moreover, doxycycline effectively regulated oncolytic adenovirus replication in the hUCB-MSCs. The doxycycline induction group with dual expression of IL24 and Endostatin exhibited significantly greater antitumor effects than other groups in a xenograft model of glioma. Thus, this strategy for systemic delivery of oncolytic adenovirus with its oncolytic activity controlled by a Tet-on system is a promising method for achieving antitumor efficacy in glioma, especially for metastatic tumors. C1 [Zhang, Junhe; Chen, Hao; Chen, Chen; Liu, Haimeng; He, Yurou; Zhao, Junli; Yang, Peiyan; Xia, Haibin] Shaanxi Normal Univ, Coll Life Sci, Dept Biochem, Lab Gene Therapy, 199 South Changan Rd, Xian 710062, Shaanxi, Peoples R China. [Zhang, Junhe] Xinxiang Med Univ, Dept Biochem & Mol Biol, Xinxiang 453003, Henan, Peoples R China. [Chen, Hao] Xi An Jiao Tong Univ, Biomed Informat & Genom Ctr, Sch Life Sci & Technol, Key Lab Biomed Informat Engn,Minist Educ, Xian 710049, Peoples R China. [Mao, Qinwen] Univ Utah, Huntsman Canc Inst, Dept Pathol, 2000 Circle Hope Dr, Salt Lake City, UT 84112 USA. C3 Shaanxi Normal University; Henan Medical University; Xi'an Jiaotong University; Utah System of Higher Education; University of Utah; Huntsman Cancer Institute RP Xia, HB (corresponding author), Shaanxi Normal Univ, Coll Life Sci, Dept Biochem, Lab Gene Therapy, 199 South Changan Rd, Xian 710062, Shaanxi, Peoples R China. EM zhangjunhe@snnu.edu.cn; chandcn_0904@126.com; 419460636@qq.com; 978551324@qq.com; hhyurou@126.com; zjlzhao2008@126.com; ufo-ypy@163.com; Qinwen.Mao@path.utah.edu; hbxia2001@163.com RI ; Zhang, Junhe/HII-7839-2022; He, Yurou/JXN-8801-2024; Chen, Hao/KIC-6174-2024 OI Chen, Hao/0000-0002-6408-9505; Xia, Haibin/0000-0002-2038-5759; Zhang, Jun-He/0000-0003-0343-0340; FU Fundamental Research Funds for the Central Universities [GK201704009]; National Natural Science Foundation of China [81773265]; Key Research and Development Plan of Shaanxi Province [2018SF106] FX This work was supported by research grants from the Fundamental Research Funds for the Central Universities (No. GK201704009) , the National Natural Science Foundation of China (No. 81773265) , and the Key Research and Development Plan of Shaanxi Province (No. 2018SF106) . 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Standard treatment modalities including surgical interventions, high-dose chemotherapy, radiotherapy, and immunotherapy are not able to increase survival rate and reduce tumor relapse in high-risk patients. Mesenchymal stem cells (MSCs) are known for their tumor-targeting and immunomodulating properties. MSCs could be engineered to express anticancer agents (i.e., growth factors, cytokines, pro-apoptotic agents) or deliver oncolytic viruses in the tumor microenvironment. As many functions of MSCs are mediated through their secretome, researchers have tried to use extracellular vesicles (EVs) from MSCs for targeted therapy of neuroblastoma. Here, we reviewed the studies to figure out whether the use of MSCs could be worthwhile in neuroblastoma therapy or not. Native MSCs have shown a promoting or inhibiting role in cancers including neuroblastoma. Therefore, MSCs are proposed as a vehicle to deliver anticancer agents such as oncolytic viruses to the neuroblastoma tumor microenvironment. Although modified MSCs or their EVs have been shown to suppress the tumorigenesis of neuroblastoma, further pre-clinical and clinical studies are required to come to a conclusion. C1 [Fath, Mohsen Karami] Kharazmi Univ, Fac Biol Sci, Dept Cellular & Mol Biol, Tehran, Iran. [Torbati, Samaneh Mohammad Bagherzadeh; Daneshdoust, Danyal] Babol Univ Med Sci, Fac Med, Babol, Iran. [Saqagandomabadi, Vahid] Univ Palermo, Dept Biomed Neurosci & Adv Diagnost, Palermo, Italy. [Afshar, Omid Yousefi] Valiasr Hosp, Clin Res Dev Unit, Tabriz, Iran. [Khalilzad, Mohammad] Tabriz Univ Med Sci, Fac Med, Tabriz, Iran. [Abedi, Sara] Univ Tabriz, Fac Nat Sci, Tabriz, Iran. [Moliani, Afshin] Isfahan Univ Med Sci, Isfahan Med Students Res Ctr, Esfahan, Iran. [Barati, Ghasem] Stem Cell Technol Res Ctr, Tehran, Iran. 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Biophys. Mol. Biol. PD MAR PY 2024 VL 187 BP 51 EP 60 DI 10.1016/j.pbiomolbio.2024.02.004 EA FEB 2024 PG 10 WC Biochemistry & Molecular Biology; Biophysics WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Biophysics GA LO6H8 UT WOS:001187779100001 PM 38373516 DA 2025-10-02 ER PT J AU Yoon, AR Hong, J Li, Y Shin, HC Lee, H Kim, HS Yun, CO AF Yoon, A-Rum Hong, JinWoo Li, Yan Shin, Ha Chul Lee, Hyunah Kim, Hyun Soo Yun, Chae-Ok TI Mesenchymal Stem Cell-Mediated Delivery of an Oncolytic Adenovirus Enhances Antitumor Efficacy in Hepatocellular Carcinoma SO CANCER RESEARCH LA English DT Article ID STROMAL CELLS; CANCER; SORAFENIB; CAPACITY; HYPOXIA; PATHWAY; SAFETY; ALPHA AB Oncolytic virotherapy is a promising alternative to conventional treatment, yet systemic delivery of these viruses to tumors remains a major challenge. In this regard, mesenchymal stem cells (MSC) with well-established tumor-homing property could serve as a promising systemic delivery tool. We showed that MSCs could be effectively infected by hepatocellular carcinoma (HCC)-targeted oncolytic adenovirus (HCC-oAd) through modification of the virus' fiber domain and that the virus replicated efficiently in the cell carrier. HCC-targeting oAd loaded in MSCs (HCC-oAd/MSC) effectively lysed HCC cells in vitro under both normoxic and hypoxic conditions as a result of the hypoxia responsiveness of HCC-oAd. Importantly, systemically administered HCC-oAd/MSC, which were initially infected with a low viral dose, homed to HCC tumors and resulted in a high level of virion accumulation in the tumors, ultimately leading to potent tumor growth inhibition. Furthermore, viral dose reduction and tumor localization of HCC-oAd/MSC prevented the induction of hepatotoxicity by attenuating HCC-oAd hepatic accumulation. Taken together, these results demonstrate that MSC-mediated systemic delivery of oAd is a promising strategy for achieving synergistic antitumor efficacy with improved safety profiles. Significance: Mesenchymal stem cells enable delivery of an oncolytic adenovirus specifically to the tumor without posing any risk associated with systemic administration of naked virions to the host. C1 [Yoon, A-Rum; Hong, JinWoo; Li, Yan; Yun, Chae-Ok] Hanyang Univ, Coll Engn, Dept Bioengn, 222 Wangsimni Ro, Seoul 04763, South Korea. [Yoon, A-Rum; Yun, Chae-Ok] Hanyang Univ, INST, Seoul, South Korea. [Hong, JinWoo; Yun, Chae-Ok] GeneMedicine CO Ltd, Seoul, South Korea. [Shin, Ha Chul; Lee, Hyunah; Kim, Hyun Soo] Pharmicell Co Ltd, Seoul, South Korea. C3 Hanyang University; Hanyang University RP Yun, CO (corresponding author), Hanyang Univ, Coll Engn, Dept Bioengn, 222 Wangsimni Ro, Seoul 04763, South Korea. EM chaeok@hanyang.ac.kr RI Yun, Chae-Ok/P-3698-2015 FU National Research Foundation of Korea [2016M3A9B5942352, 2016R1C1B2015558]; Korea Drug Development Fund (KDDF) - MSIP; MOTIE; MOHW (Republic of Korea) [KDDF-201611-05] FX This work was supported by grants from the National Research Foundation of Korea (2016M3A9B5942352 to C.-O. Yun; 2016R1C1B2015558 to A.-R. Yoon) and Korea Drug Development Fund (KDDF) funded by MSIP, MOTIE, and MOHW (KDDF-201611-05, Republic of Korea, to A.-R. Yoon). 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PD SEP 1 PY 2019 VL 79 IS 17 BP 4503 EP 4514 DI 10.1158/0008-5472.CAN-18-3900 PG 12 WC Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology GA IV2OZ UT WOS:000484117800019 PM 31289131 DA 2025-10-02 ER PT J AU Wang, PW Zhang, JW Zhang, Q Liu, FS AF Wang, Peiwen Zhang, Junwen Zhang, Qing Liu, Fusheng TI Mesenchymal stem cells loaded with Ad5-Ki67/IL-15 enhance oncolytic adenovirotherapy in experimental glioblastoma SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE Mesenchymal stem cells; Oncolytic adenovirus; Glioblastoma ID STROMAL CELLS; GLIOMA; PROLIFERATION; EXPRESSION; ADENOVIRUS; HEALTH; IL-15 AB The conventional treatment strategy for glioblastoma multiforme (GBM) is surgical resection followed by radiotherapy and chemotherapy. Oncolytic adenovirotherapy is a promising alternative to conventional treat-ment. It provides a strategic combination of direct tumor-specific cell lysis and antitumor immune promotion. Despite advances in oncolytic adenovirotherapy, limitations remain, including the host's antiviral immune response and insufficient viral infiltration into the tumor. Mesenchymal stem cells (MSCs) have emerged as innovative vehicles due to their ability to home to tumors and protect oncolytic adenovirus (oAd) from the host antiviral immune system. We developed an Ad5-Ki67/IL-15 driven by the Ki67 promoter and armed with IL-15. Using this construction, viral replication is related to Ki67 expression in GBM cells. Thus, MSCs with background Ki67 expression can help deliver higher levels of oncolytic viruses and can strike a balance between viral load and cell viability. Using in vitro assay, MSCs loaded with Ad5-Ki67/IL-15 (MSC-Ad5) were shown to exert anti-glioblastoma efficacy. Compared to previous attempts at direct intratumoral injection of high doses of viruses, MSCs loaded with lower doses of viruses exerted stronger therapeutic effects and promoted macrophage/ microglia infiltration in a Vivo model. Collectively, our results suggest that the use of MSCs as vehicles of oAd is a promising strategy and deserves further investigation for the treatment of GBM. C1 [Wang, Peiwen; Zhang, Junwen; Zhang, Qing; Liu, Fusheng] Capital Med Univ, Beijing Neurosurg Inst, Brain Tumor Res Ctr, Beijing 100070, Peoples R China. [Wang, Peiwen; Zhang, Junwen; Zhang, Qing; Liu, Fusheng] Capital Med Univ, Dept Neurosurg, Beijing Tiantan Hosp, Beijing 100070, Peoples R China. [Wang, Peiwen; Zhang, Junwen; Liu, Fusheng] Beijing Lab Biomed Mat, Beijing 100070, Peoples R China. [Zhang, Qing] Capital Med Univ, Beijing Chaoyang Hosp, Dept Neurosurg, Beijing, Peoples R China. [Liu, Fusheng] Capital Med Univ, Beijing Neurosurg Inst, Brain Tumor Res Ctr, Dept Neurosurg,Beijing Tiantan Hosp, 119 Nansihuan West Rd, Beijing 100070, Peoples R China. C3 Capital Medical University; Capital Medical University; Capital Medical University; Capital Medical University RP Liu, FS (corresponding author), Capital Med Univ, Beijing Neurosurg Inst, Brain Tumor Res Ctr, Dept Neurosurg,Beijing Tiantan Hosp, 119 Nansihuan West Rd, Beijing 100070, Peoples R China. EM liufusheng@ccmu.edu.cn RI ; Li, Zhengyan/GSD-3935-2022 OI Wang, Peiwen/0000-0003-2981-6997; FU Beijing Natural Science Foundation Program; Scientific Research Key Program of the Beijing Municipal Commission of Education [KZ202010025034]; Capital's Funds for Health Improvement and Research (CFH) [2020-1-1071]; Natural Science Foundation of Beijing Municipality [7202020]; Beijing Laboratory of Biomedical Materials Foundation FX This work was supported by grants from the Beijing Natural Science Foundation Program and Scientific Research Key Program of the Beijing Municipal Commission of Education (KZ202010025034), the Capital's Funds for Health Improvement and Research (CFH, 2020-1-1071), the Natural Science Foundation of Beijing Municipality (No. 7202020) and the Beijing Laboratory of Biomedical Materials Foundation. 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Pharmacother. PD JAN PY 2023 VL 157 AR 114035 DI 10.1016/j.biopha.2022.114035 EA NOV 2022 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 7J3AD UT WOS:000904454300001 PM 36434955 OA gold DA 2025-10-02 ER PT J AU Yang, AQ Wang, XY Jin, L Luo, HY Yang, ZR Yang, N Lin, XJ Yang, YX Zhao, X He, ZX AF Yang, Anqing Wang, Xianyao Jin, Lu Luo, Heyong Yang, Zhiru Yang, Na Lin, Xiaojin Yang, Yuxin Zhao, Xing He, Zhixu TI Human umbilical cord mesenchymal stem cell exosomes deliver potent oncolytic reovirus to acute myeloid leukemia cells SO VIROLOGY LA English DT Article DE Oncolytic reovirus; Exosome; Mesenchymal stem cells; Acute myeloid leukemia ID EXTRACELLULAR VESICLES; THERAPY; CYTOTOXICITY AB In addition to chemotherapy, oncolytic viruses are an efficient treatment for acute myeloid leukemia (AML). Like other oncolytic viruses, the anti-tumor efficacy of reovirus when administered intravenously is reduced due to the presence of neutralizing antibodies. In this study, we evaluated the role of exosomes in human umbilical cord-derived mesenchymal stem cells (UC-MSCs) to deliver reovirus to AML cells. We show that UC-MSCs loaded with reovirus can deliver reovirus to tumor cells without cellular contact. We further demonstrate that the exosome inhibitor, GW4869, inhibits the release of exosomes as well as inhibited the transfer of reovirus from UC-MSCs to tumor cells. Mechanistically, we show that exosomes derived from reovirus-infected UC-MSCs (MSCREO-EXOs) have a tumor lysis effect and transmit reovirus to tumor cells mainly through clathrin-mediated endocytosis (CME) and macropinocytosis. In addition, we demonstrate the feasibility of using MSC-derived exosomes (MSC-EXOs) as a reovirus carrier to exert an anti-tumor effect on AML cells. Collectively, our data indicate that UC-MSCs transfer reovirus to AML cells via exosome release and prompt further study of MSC-EXOs as a potential reovirus carrier to treat AML. C1 [Yang, Anqing; Jin, Lu; Luo, Heyong; Yang, Zhiru; Yang, Na; Lin, Xiaojin; Yang, Yuxin; Zhao, Xing; He, Zhixu] Guizhou Med Univ, Sch Basic Med Sci, Stem Cell & Tissue Engn Res Ctr, Guiyang, Guizhou, Peoples R China. [Yang, Anqing; Luo, Heyong; Yang, Zhiru; Yang, Na; Yang, Yuxin; Zhao, Xing; He, Zhixu] Guizhou Med Univ, Coll Basic Med Sci, Dept Immunol, Guiyang, Guizhou, Peoples R China. [Wang, Xianyao] Zunyi Med Univ, Coll Basic Med Sci, Dept Immunol, Zunyi, Guizhou, Peoples R China. [Lin, Xiaojin] Guizhou Med Univ, Sch Basic Med Sci, Dept Biol, Guiyang, Guizhou, Peoples R China. [He, Zhixu] Zunyi Med Univ, Affiliated Hosp, Dept Pediat, Zunyi, Guizhou, Peoples R China. [He, Zhixu] Chinese Acad Med Sci, Key Lab Adult Stem Cell Translat Res, Guiyang 550004, Guizhou, Peoples R China. C3 Guizhou Medical University; Guizhou Medical University; Zunyi Medical University; Guizhou Medical University; Zunyi Medical University; Chinese Academy of Medical Sciences - Peking Union Medical College RP He, ZX (corresponding author), Chinese Acad Med Sci, Key Lab Adult Stem Cell Translat Res, Guiyang 550004, Guizhou, Peoples R China.; Zhao, X (corresponding author), Guizhou Med Univ, Ctr Tissue Engn & Stem Cell Res, Guiyang 550004, Guizhou, Peoples R China. EM xingzhao@gmc.edu.cn; hzx@gmc.edu.cn RI he, zeying/HCH-3380-2022; Wang, Xianyao/LUY-2454-2024 FU National Natural Science Founda- tion of China [81871313, 32270848, 82060564]; Guizhou Province Science and Technology Project [Qian Ke He [2019] 5406]; Key Program for Science and Technology of Guizhou Province [ZK (2021) 012] FX Funding This research was funded by the National Natural Science Founda- tion of China (No. 81871313, No 32270848, No.82060564) , Guizhou Province Science and Technology Project, (Qian Ke He [2019] 5406) and Key Program for Science and Technology of Guizhou Province [grant number:ZK (2021) 012] . 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Kondo, Akihide Kerrigan, Brittany C. Parker Yang, Jing Ledbetter, Daniel Fueyo, Juan Gomez-Manzano, Candelaria Lang, Frederick F. TI Characterization of patient-derived bone marrow human mesenchymal stem cells as oncolytic virus carriers for the treatment of glioblastoma SO JOURNAL OF NEUROSURGERY LA English DT Article DE mesenchymal stem cells; glioblastoma; brain tumor; oncolytic virus; oncology AB OBJECTIVE Delta-24-RGD is an oncolytic adenovirus that is capable of replicating in and killing human glioma cells. Although intratumoral delivery of Delta-24-RGD can be effective, systemic delivery would improve its clinical applica-tion. Bone marrow-derived human mesenchymal stem cells (BM-hMSCs) obtained from healthy donors have been investigated as virus carriers. However, it is unclear whether BM-hMSCs can be derived from glioma patients previously treated with marrow-toxic chemotherapy or whether such BM-hMSCs can deliver oncolytic viruses effectively. Herein, the authors undertook a prospective clinical trial to determine the feasibility of obtaining BM-hMSCs from patients with recurrent malignant glioma who were previously exposed to marrow-toxic chemotherapy. METHODS The authors enrolled 5 consecutive patients who had been treated with radiation therapy and chemothera-py. BM aspirates were obtained from the iliac crest and were cultured to obtain BM-hMSCs. RESULTS The patient-derived BM-hMSCs (PD-BM-hMSCs) had a morphology similar to that of healthy donor-derived BM-hMSCs (HD-BM-hMSCs). Flow cytometry revealed that all 5 cell lines expressed canonical MSC surface markers. Importantly, these cultures could be made to differentiate into osteocytes, adipocytes, and chondrocytes. In all cases, the PD-BM-hMSCs homed to intracranial glioma xenografts in mice after intracarotid delivery as effectively as HD-BM-hMSCs. The PD-BM-hMSCs loaded with Delta-24-RGD (PD-BM-MSC-D24) effectively eradicated human gliomas in vitro. In in vivo studies, intravascular administration of PD-BM-MSC-D24 increased the survival of mice harboring U87MG gliomas. CONCLUSIONS The authors conclude that BM-hMSCs can be acquired from patients previously treated with marrow-toxic chemotherapy and that these PD-BM-hMSCs are effective carriers for oncolytic viruses. C1 [Shimizu, Yuzaburo; Gumin, Joy; Gao, Feng; Hossain, Anwar; Kerrigan, Brittany C. Parker; Yang, Jing; Ledbetter, Daniel; Lang, Frederick F.] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX USA. [Shpall, Elizabeth J.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Houston, TX 77030 USA. [Fueyo, Juan; Gomez-Manzano, Candelaria] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX USA. [Shimizu, Yuzaburo; Gumin, Joy; Gao, Feng; Hossain, Anwar; Kerrigan, Brittany C. Parker; Yang, Jing; Ledbetter, Daniel; Fueyo, Juan; Gomez-Manzano, Candelaria; Lang, Frederick F.] Univ Texas MD Anderson Canc Ctr, Brain Tumor Ctr, Houston, TX 77030 USA. [Shimizu, Yuzaburo; Kondo, Akihide] Juntendo Univ, Dept Neurosurg, Sch Med, Tokyo, Japan. C3 University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Juntendo University RP Lang, FF (corresponding author), Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. EM flang@mdanderson.org RI Gao, Feng/KLE-0680-2024 OI Fueyo, Juan/0000-0001-6941-2335; Gomez-Manzano, Candelaria/0000-0002-1259-2133; Parker Kerrigan, Brittany/0009-0005-9268-0342 FU National Cancer Institute [1R01CA214749, 1R01CA247970, P30CA016672, 2P50CA127001]; University of Texas MD Anderson Moon Shots Program; Broach Foundation for Brain Cancer Research; Elias Family Fund; Priscilla and Jason Hiley Fund; Baumann Family/CureFest Fund; Jim and Pam Harris Fund; Gene Pennebaker Brain Cancer Fund; Schneider Memorial Cancer Research Fund; Sweet Family Cancer Research Fund; Dr. Marnie Rose Foundation; Gold Family Memorial Fund; Sorenson Foundation FX We are grateful to Ann Sutton, Department of Scientific Pub-lications, and David Wildrick, PhD, Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, for their editorial assistance. This study was supported by the National Cancer Institute (grants nos. 1R01CA214749, 1R01CA247970, P30CA016672, and 2P50CA127001) , The University of Texas MD Anderson Moon Shots Program, The Broach Foundation for Brain Cancer Research, The Elias Family Fund, The Priscilla and Jason Hiley Fund, The Baumann Family/CureFest Fund, The Jim and Pam Harris Fund, The Gene Pennebaker Brain Cancer Fund, The Schneider Memorial Cancer Research Fund, The Sweet Family Cancer Research Fund, The Dr. Marnie Rose Foundation, The Gold Family Memorial Fund, and The Sorenson Foundation (all to F.F.L.) . 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Neurosurg. PD MAR PY 2022 VL 136 IS 3 BP 757 EP 767 DI 10.3171/2021.3.JNS203045 PG 11 WC Clinical Neurology; Surgery WE Science Citation Index Expanded (SCI-EXPANDED) SC Neurosciences & Neurology; Surgery GA VK8XZ UT WOS:000764729400002 PM 34450587 OA Bronze DA 2025-10-02 ER PT J AU Young, JS Kim, JW Ahmed, AU Lesniak, MS AF Young, Jacob S. Kim, Julius W. Ahmed, Atique U. Lesniak, Maciej S. TI Therapeutic cell carriers: a potential road to cure glioma SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE brain cancer; cell carriers; gene therapy; glioblastoma multiforme; glioma; induced progenitor cells; mesenchymal stem cells; neural stem cells; oncolytic virotherapy; tumor-tropism ID MESENCHYMAL STEM-CELLS; MULTIPLE LUNG-TUMORS; GENE-THERAPY; TARGETED-DELIVERY; ONCOLYTIC VIROTHERAPY; STROMAL CELLS; MEDIATED DELIVERY; PROGENITOR CELLS; GLIOBLASTOMA; BRAIN AB Many different experimental molecular therapeutic approaches have been evaluated in an attempt to treat brain cancer. However, despite the success of these experimental molecular therapies, research has shown that the specific and efficient delivery of therapeutic agents to tumor cells is a limitation. In this regard, cell carrier systems have garnered significant attraction due to their capacity to be loaded with therapeutic agents and carry them specifically to tumor sites. Furthermore, cell carriers can be genetically modified to express therapeutic agents that can directly eradicate cancerous cells or can modulate tumor microenvironments. This review describes the current state of cell carriers, their use as vehicles for the delivery of therapeutic agents to brain tumors, and future directions that will help overcome the present obstacles to cell carrier mediated therapy for brain cancer. C1 [Young, Jacob S.; Kim, Julius W.; Ahmed, Atique U.; Lesniak, Maciej S.] Univ Chicago, Brain Tumor Ctr, Chicago, IL 60637 USA. C3 University of Chicago RP Lesniak, MS (corresponding author), Univ Chicago, Brain Tumor Ctr, Chicago, IL 60637 USA. EM mlesniak@surgery.bsd.uchicago.edu RI Ahmed, Atique/HNS-0597-2023; Young, Jacob/AAE-6194-2020 OI Ahmed, Atique/0000-0003-4795-0188; FU NIH [R01CA122930, R01CA138587, R01NS077388, U01NS069997] FX This work is supported by NIH grants R01CA122930, R01CA138587, R01NS077388 and U01NS069997. 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Neurother. PD JUN PY 2014 VL 14 IS 6 BP 651 EP 660 DI 10.1586/14737175.2014.917964 PG 10 WC Clinical Neurology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Neurosciences & Neurology; Pharmacology & Pharmacy GA AJ4WR UT WOS:000337680200008 PM 24852229 DA 2025-10-02 ER PT J AU Morales-Molina, A Rodriguez-Milla, MA Gambera, S Cejalvo, T de Andres, B Gaspar, ML Garcia-Castro, J AF Morales-Molina, Alvaro Rodriguez-Milla, Miguel angel Gambera, Stefano Cejalvo, Teresa de Andres, Belen Gaspar, Maria-Luisa Garcia-Castro, Javier TI Toll-like Receptor Signaling-deficient Cells Enhance Antitumor Activity of Cell-based Immunotherapy by Increasing Tumor Homing SO CANCER RESEARCH COMMUNICATIONS LA English DT Article ID MESENCHYMAL STEM-CELLS; ONCOLYTIC VIROTHERAPY; ADVERSE EVENTS; DELIVERY; NEUROBLASTOMA; ICOVIR-5; CARRIER AB Cancer immunotherapy aims to activate the immune system. Some im-munotherapeutic agents can be loaded in carrier cells for delivering to the tumors. However, a challenge with cell-based therapies is the selection of the appropriate cells to produce effective clinical outcomes. We hypothesize that therapies based on cells presenting a natural low proinflammatory pro-file ("silent cells") in the peripheral blood would result in better antitumor responses by increasing their homing to the tumor site. We studied our hy-pothesis in an immunotherapy model consisting of mesenchymal stromal cells (MSCs) carrying oncolytic adenoviruses for the treatment of immuno-competent mice. Toll-like receptor signaling-deficient cells (TLR4, TLR9, or MyD88 knockout) were used as "silent cells," while regular MSCs were used as control. Although in vitro migration was similar in regular and knockout carrier cells, in vivo tumor homing of silent cells was significantly higher after systemic administration. This better homing to the tumor site was highly related to the mild immune response triggered by these silent cells in peripheral blood. As a result, the use of silent cells significantly im- proved the antitumor efficacy of the treatment in comparison with the use of regular MSCs. While cancer immunotherapies generally aim to boost local immune responses in the tumor microenvironment, low systemic inflammation after systemic administration of the treatment may indeed enhance their tumor homing and improve the overall antitumor effect. These findings highlight the importance of selecting appropriate donor cells therapeutic carriers in cell-based therapies for cancer treatment. Significance: Cells carrying drugs, virus, or other antitumor agents are commonly used for the treatment of cancer. This research shows that silent cells are excellent carriers for immunotherapies, improving tumor homing and enhancing the antitumor effect. C1 [Morales-Molina, Alvaro; Rodriguez-Milla, Miguel angel; Gambera, Stefano; Cejalvo, Teresa; Garcia-Castro, Javier] Inst Invest Enfermedades Raras, Inst Salud Carlos ISCIII 3, Cellular Biotechnol Unit, Madrid, Spain. [Gambera, Stefano] Ctr Nacl Invest Cardiovasc CN, Mol Genet Angiogenesis Grp, Madrid, Spain. [Cejalvo, Teresa] AEMPS, Dept Med Human Use, Biol Prod Adv Therapies & Biotechnol, Madrid, Spain. [de Andres, Belen; Gaspar, Maria-Luisa] Inst Salud Carlos III ISCIII, Immunol Lab, Ctr Nacl Microbiol, Majadahonda, Spain. [Garcia-Castro, Javier] Inst Salud Carlos III, Avda Majadahonda-Pozuelo, Km 2, Madrid 28220, Spain. C3 Instituto de Salud Carlos III; Instituto de Investigacion de Enfermedades Raras (IIER); Instituto de Salud Carlos III; Centro Nacional de Microbiologia (CNM); Instituto de Salud Carlos III RP Garcia-Castro, J (corresponding author), Inst Salud Carlos III, Avda Majadahonda-Pozuelo, Km 2, Madrid 28220, Spain. EM jgcastro@isciii.es RI Garcia-Castro, Javier/H-5274-2011; Gaspar, Maria Luisa/P-5436-2014; Gambera, Stefano/X-8631-2019; Rodriguez, Miguel/L-7340-2014; Ruiz Sanchez, Carolina/HTL-9286-2023; De Andrés, Belen/D-4712-2016; Ruiz, Carolina/HTL-9286-2023 OI Garcia-Castro, Javier/0000-0001-7604-1640; Gaspar, Maria Luisa/0000-0001-9858-3862; Rodriguez, Miguel/0000-0002-2640-5888; Ruiz Sanchez, Carolina/0000-0002-2177-8132; Morales-Molina, Alvaro/0000-0003-4532-7667; DE ANDRES, BELEN/0000-0002-7391-2823; FU Instituto de Salud Carlos III [PI14CIII/00005, PI17CIII/00013, ISCIII-PFIS FI18CIII/00017]; Consejeria de Educacin, Juventud y Deporte of Comunidad de Madrid [P2017/BMD-3692]; Fundacion Oncohematologia Infantil, Asociacion Pablo Ugarte; AFANION FX This study was funded by Instituto de Salud Carlos III (grants PI14CIII/00005, PI17CIII/00013, and ISCIII-PFIS FI18CIII/00017) , Consejeria de Educacion, Juventud y Deporte of Comunidad de Madrid (grant P2017/BMD-3692) , Fundacion Oncohematologia Infantil, Asociacion Pablo Ugarte and AFANION, whose support we gratefully acknowledge. 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Mesenchymal stem cells (MSCs) are good carriers because of their tumor tropic and immune-evasive capabilities. We collated published results from pre-clinical and clinical trials to support the use of MSCs as Trojan horses for the systemic administration of recombinant viruses, with a focus on glioblastoma. The generation of modified MSCs harboring recombinant viruses could expedite bench-to-bedside transformation. C1 [Tahir, Muhammad] Beijing Univ Technol, Fac Environm & Life, Beijing 100124, Peoples R China. [Ahmad, Nadeem] COMSATS Univ Islamabad, Dept Pharm, Abbottabad Campus, Abbottabad 22060, Pakistan. [Lei, Dong; Ali, Sakhawat] Beijing Inst Technol, Sch Life Sci, Beijing 100081, Peoples R China. C3 Beijing University of Technology; COMSATS University Islamabad (CUI); Beijing Institute of Technology RP Ali, S (corresponding author), Beijing Inst Technol, Sch Life Sci, Beijing 100081, Peoples R China. 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Today PD AUG PY 2022 VL 27 IS 8 BP 2244 EP 2251 DI 10.1016/j.drudis.2022.03.016 PG 8 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 2N9JP UT WOS:000818687600020 PM 35351608 DA 2025-10-02 ER PT J AU Na, YJ Nam, JP Hong, J Oh, E Shin, HC Kim, HS Kim, SW Yun, CO AF Na, Youjin Nam, Joung-Pyo Hong, JinWoo Oh, Eonju Shin, Ha Cheol Kim, Hyun Soo Kim, Sung Wan Yun, Chae-Ok TI Systemic administration of human mesenchymal stromal cells infected with polymer-coated oncolytic adenovirus induces efficient pancreatic tumor homing and infiltration SO JOURNAL OF CONTROLLED RELEASE LA English DT Article; Proceedings Paper CT 5th Symposium on Innovative Polymers for Controlled Delivery (SIPCD) CY SEP 14-17, 2018 CL Suzhou, PEOPLES R CHINA DE Oncolytic adenovirus; Mesenchymal stromal cell; Gene therapy; Pancreatic cancer; Relaxin ID STEM-CELLS; GENE DELIVERY; ANTITUMOR EFFICACY; TARGETED-DELIVERY; PROGENITOR CELLS; MODIFIED FIBERS; DENDRIMER; VEHICLES; CARRIERS; VECTORS AB Oncolytic adenovirus (oAd)-mediated gene therapy is a promising approach for cancer treatment because of its cancer cell-restricted replication and therapeutic gene expression. However, systemic administration of oAd is severely restricted by their immunogenic nature and poor tumor homing ability, thus oAd cannot be utilized to treat disseminated metastases. In this study, human bone marrow-derived mesenchymal stromal cell (hMSCs) was used as a viral replication-permissive carrier for oAd with an aim to improve the systemic delivery of the virus to tumor tissues. To overcome the poor delivery of oAd into hMSCs, a relaxin (RLX)-expressing oncolytic Ad (oAd/RLX), which degrades dense tumor extracellular matrix of highly desmoplastic pancreatic cancer, was complexed with biodegradable polymer (poly (ethyleneimine)-conjugated poly(CBA-DAH); PCDP), generating oAd/RLX-PCDP complex. oAd/RLX-PCDP complex enhanced the internalization of oAd into hMSC, leading to superior viral production and release from hMSCs, along with high RLX expression. Furthermore, systemic administration of oAd/RLX-PCDP-treated hMSCs elicited more potent antitumor effect compared to naked oAd/RLX or oAd/RLX-treated hMSC in pancreatic tumor model. This potent antitumor effect of systemically administered oAd/RLX-PCDP-treated hMSCs was achieved by superior viral replication in tumor tissues than any other treatment group. In conclusion, these results demonstrate that hMSCs are effective carriers for the systemic delivery of oAd to tumor sites and treatment of pancreatic cancer. C1 [Na, Youjin; Nam, Joung-Pyo; Kim, Sung Wan] Univ Utah, Ctr Controlled Chem Delivery, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84112 USA. [Hong, JinWoo; Oh, Eonju; Yun, Chae-Ok] Hanyang Univ, Coll Engn, Dept Bioengn, 222 Wangsinmi Ro, Seoul, South Korea. [Shin, Ha Cheol; Kim, Hyun Soo] Pharmicell Co Ltd, Sugnam, South Korea. C3 Utah System of Higher Education; University of Utah; Hanyang University RP Yun, CO (corresponding author), Hanyang Univ, Coll Engn, Dept Bioengn, 222 Wangsinmi Ro, Seoul, South Korea. EM chaeok@hanyang.ac.kr RI Yun, Chae-Ok/P-3698-2015 FU National Institutes of Health, USA [CA177932]; KIM; National Research Foundation of Korea [2016M3A9B5942352] FX This work was supported by grants from the National Institutes of Health, USA (CA177932) to Dr. SW. KIM. Additional supports were provided by grants from the National Research Foundation of Korea to Dr. Chae-Ok Yun (2016M3A9B5942352). We are grateful to Pharmicell Co. Ltd., Sungnam, South Korea, for providing hMSCs from a healthy donor. 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Control. Release PD JUL 10 PY 2019 VL 305 BP 75 EP 88 DI 10.1016/j.jconrel.2019.04.040 PG 14 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED); Conference Proceedings Citation Index - Science (CPCI-S) SC Chemistry; Pharmacology & Pharmacy GA IF3QE UT WOS:000472996600007 PM 31071373 OA Green Accepted DA 2025-10-02 ER PT J AU Kwon, S Yoo, KH Sym, SJ Khang, D AF Kwon, Song Yoo, Kwai Han Sym, Sun Jin Khang, Dongwoo TI Mesenchymal stem cell therapy assisted by nanotechnology: a possible combinational treatment for brain tumor and central nerve regeneration SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Review DE glioblastoma multiforme; tumor inhibition; mesenchymal stem cell; nanocarrier; nerve regeneration; anti-inflammation ID MARROW STROMAL CELLS; REGULATORY T-CELLS; BLOOD-BRAIN; IN-VITRO; GLIOBLASTOMA-MULTIFORME; ONCOLYTIC ADENOVIRUS; DRUG-DELIVERY; NANOPARTICLE HYPERTHERMIA; MACROPHAGE PLASTICITY; ABC TRANSPORTERS AB Mesenchymal stem cells (MSCs) intrinsically possess unique features that not only help in their migration towards the tumor-rich environment but they also secrete versatile types of secretomes to induce nerve regeneration and analgesic effects at inflammatory sites. As a matter of course, engineering MSCs to enhance their intrinsic abilities is growing in interest in the oncology and regenerative field. However, the concern of possible tumorigenesis of genetically modified MSCs prompted the development of non-viral transfected MSCs armed with nanotechnology for more effective cancer and regenerative treatment. Despite the fact that a large number of successful studies have expanded our current knowledge in tumor-specific targeting, targeting damaged brain site remains enigmatic due to the presence of a blood-brain barrier (BBB). A BBB is a barrier that separates blood from brain, but MSCs with intrinsic features of transmigration across the BBB can efficiently deliver desired drugs to target sites. Importantly, MSCs, when mediated by nanoparticles, can further enhance tumor tropism and can regenerate the damaged neurons in the central nervous system through the promotion of axon growth. This review highlights the homing and nerve regenerative abilities of MSCs in order to provide a better understanding of potential cell therapeutic applications of non-genetically engineered MSCs with the aid of nanotechnology. C1 [Kwon, Song; Khang, Dongwoo] Gachon Univ, Lee Gil Ya Canc & Diabet Inst, Incheon 21999, South Korea. [Yoo, Kwai Han; Sym, Sun Jin] Gachon Univ, Sch Med, Div Hematol, Dept Internal Med,Gil Med Ctr, Incheon 21565, South Korea. [Khang, Dongwoo] Gachon Univ, Dept Gachon Adv Inst Hlth Sci & Technol GAIHST, Incheon 21999, South Korea. [Khang, Dongwoo] Gachon Univ, Sch Med, Dept Physiol, Incheon 21999, South Korea. C3 Gachon University; Gachon University; Gachon University; Gachon University RP Khang, D (corresponding author), Gachon Univ, Sch Med, Dept Physiol, Incheon 21999, South Korea.; Sym, SJ (corresponding author), Gachon Univ, Sch Med, Div Hematol & Oncol, Incheon 21565, South Korea.; Sym, SJ (corresponding author), Gil Hosp, Incheon 21565, South Korea. EM sympson@gilhospital.com; dkhang@gachon.ac.kr OI Khang, Dongwoo/0000-0003-2353-8017 FU Gachon University [2017-0180]; Gil Medical Center Research Fund [2018-5295] FX This research was supported by grants from Gachon University of Funds (2017-0180) and Gil Medical Center Research Fund (2018-5295). 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J. Nanomed. PY 2019 VL 14 BP 5925 EP 5942 DI 10.2147/IJN.S217923 PG 18 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA IM5UN UT WOS:000478059200002 PM 31534331 OA Green Published, gold DA 2025-10-02 ER PT J AU Jiang, H Gomez-Manzano, C Lang, FF Alemany, R Fueyo, J AF Jiang, Hong Gomez-Manzano, Candelaria Lang, Frederick F. Alemany, Ramon Fueyo, Juan TI Oncolytic Adenovirus: Preclinical and Clinical Studies in Patients with Human Malignant Gliomas SO CURRENT GENE THERAPY LA English DT Review ID MESENCHYMAL STEM-CELLS; BRAIN; DELIVERY; PATHWAY; TUMORS; TRIAL; IDENTIFICATION; GLIOBLASTOMAS; TEMOZOLOMIDE; REPLICATION AB Oncolytic adenoviruses are emerging as a promising alternative therapy for glioma patients and are currently being tested in clinic. In this review, we summarize our experience with gene-based therapy targeting RB pathway in gliomas. Our study has evolved from the development of RB-expressing adenoviral vectors to the characterization of the oncolytic effects on gliomas of the replication competent adenoviruses Delta-24, Delta-24-RGD and ICOVIR. We also review the successful combination of the viruses with chemotherapies that are routinely used in glioma patients, the efficacy of Delta-24-RGD against brain tumor stem cells, the newly described adenovirus-induced autophagy and the potential for the systemic delivery of the oncolytic viruses with human mesenchymal stem cells. Finally, we comment on the preclinical and clinical studies of p53 expressing adenoviral vector and the lessons learned from the experience of Onyx-015, the first oncolytic adenovirus tested in clinical setting. C1 [Jiang, Hong; Gomez-Manzano, Candelaria; Lang, Frederick F.; Alemany, Ramon; Fueyo, Juan] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. C3 University of Texas System; UTMD Anderson Cancer Center RP Jiang, H (corresponding author), Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. EM hjiang@mdanderson.org OI Gomez-Manzano, Candelaria/0000-0002-1259-2133; Fueyo, Juan/0000-0001-6941-2335 FU NIH [P50CA127001]; Marcus Foundation FX This work was partially supported by the NIH/P50CA127001 award and the Marcus Foundation. 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TI TGF-β Mediates Homing of Bone Marrow-Derived Human Mesenchymal Stem Cells to Glioma Stem Cells SO CANCER RESEARCH LA English DT Article ID TUMORS; MIGRATION; TROPISM; PLASMA AB Although studies have suggested that bone marrow human mesenchymal stem cells (BM-hMSC) may be used as delivery vehicles for cancer therapy, it remains unclear whether BM-hMSCs are capable of targeting cancer stem cells, including glioma stem cells (GSC), which are the tumor-initiating cells responsible for treatment failures. Using standard glioma models, we identify TGF-beta as a tumor factor that attracts BM-hMSCs via TGF-beta receptors (TGF beta R) on BM-hMSCs. Using human and rat GSCs, we then show for the first time that intravascularly administered BM-hMSCs home to GSC-xenografts that express TGF-beta. In therapeutic studies, we show that BM-hMSCs carrying the oncolytic adenovirus Delta-24-RGD prolonged the survival of TGF-beta-secreting GSC xenografts and that the efficacy of this strategy can be abrogated by inhibition of TGFbR on BM-hMSCs. These findings reveal the TGF-beta/TGF beta R axis as a mediator of the tropism of BM-hMSCs for GSCs and suggest that TGF-beta predicts patients in whom BM-hMSC delivery will be effective. Cancer Res; 73(7); 2333-44. (C)2012 AACR. C1 [Shinojima, Naoki; Hossain, Anwar; Takezaki, Tatsuya; Gumin, Joy; Gao, Feng; Nwajei, Felix; Lang, Frederick F.] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. [Fueyo, Juan] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Marini, Frank C.; Andreeff, Michael] Univ Texas MD Anderson Canc Ctr, Dept Mol Hematol & Therapy, Houston, TX 77030 USA. [Shinojima, Naoki; Hossain, Anwar; Takezaki, Tatsuya; Fueyo, Juan; Gumin, Joy; Gao, Feng; Nwajei, Felix; Lang, Frederick F.] Univ Texas MD Anderson Canc Ctr, Brain Tumor Ctr, Houston, TX 77030 USA. [Shinojima, Naoki; Takezaki, Tatsuya; Kuratsu, Jun-Ichi] Kumamoto Univ, Dept Neurosurg, Grad Sch Life Sci, Kumamoto, Japan. C3 University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; Kumamoto University RP Lang, FF (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Box 442,1515 Holcombe Blvd, Houston, TX 77030 USA. EM flang@mdanderson.org RI ; Gao, Feng/KLE-0680-2024; Shinojima, Naoki/AAW-3038-2021; Marini, Frank/L-8018-2016 OI Fueyo, Juan/0000-0001-6941-2335; Shinojima, Naoki/0000-0003-3352-7936; FU National Cancer Institute [CA115729, 1P50 CA127001]; Ben and Catherine Ivy Foundation; Broach Foundation for Brain Cancer Research; MD Anderson Center for Targeted Therapy; National Brain Tumor Foundation; Collaborative Ependymoma Research Network (CERN); Elias Family Fund, The Gene Pennebaker Brain Cancer Fund, the Sorenson Foundation, and the Brian McCulloch Fund; Grants-in-Aid for Scientific Research [23390351, 25293312] Funding Source: KAKEN FX This study was supported by grants from the National Cancer Institute CA115729 and 1P50 CA127001, The Ben and Catherine Ivy Foundation, The Broach Foundation for Brain Cancer Research, MD Anderson Center for Targeted Therapy, The National Brain Tumor Foundation, The Collaborative Ependymoma Research Network (CERN), The Elias Family Fund, The Gene Pennebaker Brain Cancer Fund, the Sorenson Foundation, and the Brian McCulloch Fund to F.F. 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PD APR 1 PY 2013 VL 73 IS 7 BP 2333 EP 2344 DI 10.1158/0008-5472.CAN-12-3086 PG 12 WC Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology GA 118AU UT WOS:000316995600030 PM 23365134 OA Green Submitted, Bronze DA 2025-10-02 ER PT J AU Moreno, R AF Moreno, Rafael TI Mesenchymal stem cells and oncolytic viruses: joining forces against cancer SO JOURNAL FOR IMMUNOTHERAPY OF CANCER LA English DT Review DE immunomodulation; oncolytic viruses; cell engineering; oncolytic virotherapy ID STROMAL CELLS; IMMUNOLOGICAL-PROPERTIES; MEASLES-VIRUS; BONE-MARROW; DELIVERY; CARRIERS; LUNG; ADENOVIRUSES; MECHANISMS; DIFFERENTIATION AB The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving approval for some indications. Recently, OVs have also gathered interest as candidates to use in combination with immunotherapies for cancer due to their immunogenic properties, which include immunogenic cell death and the possibility to carry therapeutic transgenes in their genomes. OVs transform non-immunogenic 'cold' tumors into inflamed immunogenic 'hot' tumors, where immunotherapies show the highest efficacy. However, in monotherapy or in combination with immunotherapy, OVs face numerous challenges that limit their successful application, in particular upon systemic administration, such as liver sequestration, neutralizing interactions in blood, physical barriers to infection, and fast clearance by the immune system. In this regard, the use of mesenchymal stem cells (MSCs) as cells carrier for OV delivery addresses many of these obstacles acting as virus carriers and factories, expressing additional transgenes, and modulating the immune system. Here, I review the current progress of OVs-loaded MSCs in cancer, focusing on their interaction with the immune system, and discuss new strategies to improve their therapeutic efficacy. C1 [Moreno, Rafael] Catalan Inst Oncol ICO, ProCURE Program, Virotherapy & Immunotherapy Grp, Lhospitalet De Llobregat, Spain. [Moreno, Rafael] Inst Invest Biomed Bellvitge IDIBELL, Oncobell Program, Canc Virotherapy Grp, Lhospitalet De Llobregat, Spain. C3 Institut Catala d'Oncologia; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL) RP Moreno, R (corresponding author), Catalan Inst Oncol ICO, ProCURE Program, Virotherapy & Immunotherapy Grp, Lhospitalet De Llobregat, Spain.; Moreno, R (corresponding author), Inst Invest Biomed Bellvitge IDIBELL, Oncobell Program, Canc Virotherapy Grp, Lhospitalet De Llobregat, Spain. 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Cancer PY 2021 VL 9 IS 2 AR e001684 DI 10.1136/jitc-2020-001684 PG 9 WC Oncology; Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Immunology GA QG3SF UT WOS:000617508400004 PM 33558278 OA Green Published, gold DA 2025-10-02 ER PT J AU Moreno, R Fajardo, CA Farrera-Sal, M Perise-Barrios, AJ Morales-Molina, A Al-Zaher, AA Garcia-Castro, J Alemany, R AF Moreno, Rafael Alberto Fajardo, Carlos Farrera-Sal, Marti Judith Perise-Barrios, Ana Morales-Molina, Alvaro Abdullah Al-Zaher, Ahmed Garcia-Castro, Javier Alemany, Ramon TI Enhanced Antitumor Efficacy of Oncolytic Adenovirus-loaded Menstrual Blood-derived Mesenchymal Stem Cells in Combination with Peripheral Blood Mononuclear Cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID INNATE IMMUNE-RESPONSE; STROMAL CELLS; IN-VIVO; ACTIVATION; DELIVERY; VECTORS; IMMUNOMODULATION; DIFFERENTIATION; NEUROBLASTOMA; MODULATION AB Several studies have evaluated the efficacy of using human oncolytic adenovirus (OAdv)-loaded mesenchymal stem cells (MSC) for cancer treatment. For example, we have described the antitumor efficacy of CELYVIR, autologous bone marrow-mesenchymal stem cells infected with the OAdv ICOVIR-5, for treatment of patients with neuroblastoma. Results from this clinical trial point out the role of the immune system in the clinical outcome. In this context, a better understanding of the immunophenotypic changes of human MSCs upon adenoviral infection and how these changes affect human autologous or allogeneic peripheral blood mononuclear cells (PBMC) could guide strategies to improve the antitumor efficacy of infected MSCs. In this work, we show how infection by an OAdv induces toll-like receptor 9 overexpression and activation of the NFB pathway in menstrual blood-derived MSCs, leading to a specific cytokine secretion profile. Moreover, a proinflammatory environment, mainly mediated by monocyte activation that leads to the activation of both T cells and natural killer cells (NK cell), is generated when OAdv-loaded MSCs are cocultured with allogeneic PBMCs. This combination of allogeneic PBMCs and OAdv-loaded MSCs enhances antitumor efficacy both in vitro and in vivo, an effect partially mediated by monocytes and NK cells. Altogether our results demonstrate not only the importance of the immune system for the OAdv- loaded MSCs antitumor efficacy, but in particular the benefits of using allogeneic MSCs for this therapy. C1 [Moreno, Rafael; Alberto Fajardo, Carlos; Farrera-Sal, Marti; Abdullah Al-Zaher, Ahmed; Alemany, Ramon] Inst Catalan Oncol IDIBELL, Virotherapy & Gene therapy Grp, ProCure Program, Translat Res Lab, Barcelona, Spain. VCN Biosci SL, Grifols Corp Off, Sant Cugat Del Valles, Spain. [Judith Perise-Barrios, Ana; Morales-Molina, Alvaro; Garcia-Castro, Javier] Inst Hlth Carlos III ISCIII, Cellular Biotechnol Unit, Madrid, Spain. C3 Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); Institut Catala d'Oncologia RP Moreno, R (corresponding author), IDIBELL Inst Catalan Oncol IDIBELL, Gran Via lHospitalet 199, Barcelona 08908, Spain. EM rafamoreno@iconcologia.net RI ; Garcia-Castro, Javier/H-5274-2011; Perisé Barrios, Ana Judith/A-4007-2019; Garcia-Castro, Javier/ABC-9741-2021 OI Perise Barrios, Ana Judith/0000-0002-0136-3968; Garcia-Castro, Javier/0000-0001-7604-1640; Farrera Sal, Marti/0000-0002-8170-1276; Morales-Molina, Alvaro/0000-0003-4532-7667; Fajardo, Carlos Alberto/0000-0003-4635-2645 FU Asociacion Espanola Contra el Cancer (AECC) [BIO2014-57716-C2-1-R]; Ministerio de Economia y Competitividad of Spain [PI14CIII/00005, PI17CIII/00013, BIO2015-68990-REDT]; Red ADVANCE(CAT) project from Ris3CAT [COMRDI15-1-0013]; Generalitat de Catalunya [2014SGR364]; European Regional Development Fund, a way to Build Europe FX The authors thank Jana de Sostoa, Dolores Ramos, and Silvia Torres for their lab technical support. We also thank Vanessa Cervera for samples processing. We are grateful to Ashleigh Jones for grammatical and style proofreading. This work was supported by Asociacion Espanola Contra el Cancer (AECC), BIO2014-57716-C2-1-R grant (to R. Alemany) and PI14CIII/00005 and PI17CIII/00013 (to J. Garcia-Castro) from the Ministerio de Economia y Competitividad of Spain, Adenonet BIO2015-68990-REDT from the Ministerio de Economia y Competitividad of Spain, Red ADVANCE(CAT) project COMRDI15-1-0013 from Ris3CAT, and 2014SGR364 research grant from the 'Generalitat de Catalunya,' and cofunded by the European Regional Development Fund, a way to Build Europe (all to R. Alemany). CR Fajardo CA, 2017, CANCER RES, V77, P2052, DOI 10.1158/0008-5472.CAN-16-1708 Alcayaga-Miranda F, 2015, STEM CELL RES THER, V6, DOI 10.1186/s13287-015-0013-5 Appledorn DM, 2008, J IMMUNOL, V181, P2134, DOI 10.4049/jimmunol.181.3.2134 Bunnell BA, 2010, STEM CELL RES THER, V1, DOI 10.1186/scrt34 Calandra T, 2003, NAT REV IMMUNOL, V3, P791, DOI 10.1038/nri1200 Cascallo M, 2007, MOL THER, V15, P1607, DOI 10.1038/sj.mt.6300239 Cejalvo T, 2018, CANCER RES, V78, P4891, DOI [10.1158/0008-5472.CAN-17-3754, 10.1158/0008-5472.can-17-3754] Cerullo V, 2007, MOL THER, V15, P378, DOI 10.1038/sj.mt.6300031 Darzi S, 2016, STEM CELL TRANSL MED, V5, P1127, DOI 10.5966/sctm.2015-0190 Eichholz K, 2016, PLOS PATHOG, V12, DOI 10.1371/journal.ppat.1005871 Eriksson E, 2017, CLIN CANCER RES, V23, P5846, DOI 10.1158/1078-0432.CCR-17-0285 García-Castro J, 2010, CANCER GENE THER, V17, P476, DOI 10.1038/cgt.2010.4 Gasteiger G, 2014, NAT REV IMMUNOL, V14, P631, DOI 10.1038/nri3726 Gebler A, 2012, TRENDS MOL MED, V18, P128, DOI 10.1016/j.molmed.2011.10.004 Gupta KK, 2016, BIOCHEM BIOPH RES CO, V477, P503, DOI 10.1016/j.bbrc.2016.06.065 Hakkarainen T, 2007, HUM GENE THER, V18, P627, DOI 10.1089/hum.2007.034 Kasono K, 1999, CLIN CANCER RES, V5, P2571 Kidd S, 2010, CYTOTHERAPY, V12, P615, DOI 10.3109/14653241003631815 Alfano AL, 2017, MOL THER-ONCOLYTICS, V6, P31, DOI 10.1016/j.omto.2017.06.002 Lee AJ, 2017, J EXP MED, V214, P1153, DOI 10.1084/jem.20160880 Liu Q, 2003, GENE THER, V10, P935, DOI 10.1038/sj.gt.3302036 Lyakh LA, 2002, BLOOD, V99, P600, DOI 10.1182/blood.V99.2.600 Melen GJ, 2016, CANCER LETT, V371, P161, DOI 10.1016/j.canlet.2015.11.036 Michel T, 2013, FRONT IMMUNOL, V3, DOI 10.3389/fimmu.2012.00403 Moreno R, 2017, STEM CELLS INT, V2017, DOI 10.1155/2017/3615729 Najar M, 2017, IMMUNE NETW, V17, P89 Najar M, 2016, J IMMUNOTHER, V39, P45, DOI 10.1097/CJI.0000000000000108 Najar M, 2016, CYTOTHERAPY, V18, P160, DOI 10.1016/j.jcyt.2015.10.011 Rodrigues MCO, 2016, ADV EXP MED BIOL, V951, P111, DOI 10.1007/978-3-319-45457-3_9 Parrish C, 2015, LEUKEMIA, V29, P1799, DOI 10.1038/leu.2015.88 Ribas A, 2017, CELL, V170, P1109, DOI 10.1016/j.cell.2017.08.027 Rincón E, 2017, ONCOTARGET, V8, P45415, DOI 10.18632/oncotarget.17557 Rodríguez-García A, 2015, CLIN CANCER RES, V21, P1406, DOI 10.1158/1078-0432.CCR-14-2213 Rojas JJ, 2010, MOL THER, V18, P1960, DOI 10.1038/mt.2010.173 Romieu-Mourez R, 2009, J IMMUNOL, V182, P7963, DOI 10.4049/jimmunol.0803864 Sangiorgi B, 2016, STEM CELLS INT, V2016, DOI 10.1155/2016/9434250 Tähtinen S, 2016, J IMMUNOTHER, V39, P343 Tanoue K, 2017, CANCER RES, V77, P2040, DOI 10.1158/0008-5472.CAN-16-1577 Teigler JE, 2014, J VIROL, V88, P10354, DOI 10.1128/JVI.00936-14 Uchibori R, 2014, INT J HEMATOL, V99, P377, DOI 10.1007/s12185-014-1537-7 Waterman RS, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0045590 Waterman RS, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0010088 Wilson AA, 2013, MOL THER, V21, P825, DOI 10.1038/mt.2013.19 Woller N, 2015, MOL THER, V23, P1630, DOI 10.1038/mt.2015.115 Yuan XF, 2016, CANCER LETT, V381, P85, DOI 10.1016/j.canlet.2016.07.019 Zhu JG, 2007, J VIROL, V81, P3170, DOI 10.1128/JVI.02192-06 NR 46 TC 38 Z9 40 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2019 VL 18 IS 1 BP 127 EP 138 DI 10.1158/1535-7163.MCT-18-0431 PG 12 WC Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology GA HG2YY UT WOS:000454836100011 PM 30322950 DA 2025-10-02 ER PT J AU Guo, Y Zhang, ZZ Xu, XG Xu, ZY Wang, SB Huang, DS Li, YF Mou, XZ Liu, FL Xiang, C AF Guo, Yang Zhang, Zhenzhen Xu, Xiaogang Xu, Zhenyu Wang, Shibing Huang, Dongsheng Li, Yifei Mou, Xiaozhou Liu, Fanlong Xiang, Charlie TI Menstrual Blood-Derived Stem Cells as Delivery Vehicles for Oncolytic Adenovirus Virotherapy for Colorectal Cancer SO STEM CELLS AND DEVELOPMENT LA English DT Article DE menstrual blood-derived mesenchymal stem cells; colorectal cancer; oncolytic viral therapy ID PROGENITOR CELLS; VIRUS THERAPY; BONE-MARROW; EXOSOMES; LIVER; BIODISTRIBUTION; BREAST; TUMOR; RECEPTOR; VECTORS AB Oncolytic adenoviruses (Ads) have potential applications in cancer therapy due to their ability to replicate and induce tumor cell death. However, their clinical application has been limited by the lack of efficient cell-based delivery systems that can provide protection from immune attack and prevent virus clearance by neutralizing antibodies. We previously demonstrated that menstrual blood-derived mesenchymal stem cells (MenSCs) can specifically target tumor cells and serve as a novel drug delivery platform. We engineered CRAd5/F11 chimeric oncolytic Ads that can infect MenSCs and preserve their tumor targeting ability in vitro. MenSCs loaded with these Ads were transplanted in a mouse tumor model. We found that a large number of the CRAd5/F11 viruses were accumulated in tumor site and mediated marked inhibitory effects against colorectal cancer (CRC). Thus, we concluded that MenSC-cloaked oncolytic Ads hold great potential as a novel virus-delivery platform for the therapy of various cancers, including CRC. C1 [Guo, Yang; Zhang, Zhenzhen; Xu, Zhenyu; Xiang, Charlie] Zhejiang Univ, Sch Med, State Key Lab Diag & Treatment Infect Dis, 866 Yuhangtang Rd, Hangzhou 310003, Zhejiang, Peoples R China. [Xu, Xiaogang] Zhejiang Hosp, Hangzhou, Zhejiang, Peoples R China. [Xu, Xiaogang] Zhejiang Prov Key Lab Geriatr, Hangzhou, Zhejiang, Peoples R China. [Wang, Shibing; Huang, Dongsheng; Mou, Xiaozhou] Hangzhou Med Coll, Peoples Hosp, Zhejiang Prov Peoples Hosp, Clin Res Inst, 158 Shangtang Rd, Hangzhou 310014, Zhejiang, Peoples R China. [Wang, Shibing; Huang, Dongsheng; Mou, Xiaozhou] Key Lab Tumor Mol Diag & Individualized Med Zheji, Hangzhou, Zhejiang, Peoples R China. [Li, Yifei; Xiang, Charlie] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Collaborat Innovat Ctr Diag & Treatment Infect Di, Hangzhou, Zhejiang, Peoples R China. [Liu, Fanlong] Zhejiang Univ, Affiliated Hosp 1, Dept Colorectal & Anal Surg, 79 Qingchun Rd, Hangzhou 310003, Zhejiang, Peoples R China. C3 Zhejiang University; Hangzhou Medical College; Zhejiang Provincial People's Hospital; Zhejiang University; Collaborative Innovation Center for Diagnosis & Treatment of Infectious Diseases; Zhejiang University RP Xiang, C (corresponding author), Zhejiang Univ, Sch Med, State Key Lab Diag & Treatment Infect Dis, 866 Yuhangtang Rd, Hangzhou 310003, Zhejiang, Peoples R China.; Mou, XZ (corresponding author), Hangzhou Med Coll, Peoples Hosp, Zhejiang Prov Peoples Hosp, Clin Res Inst, 158 Shangtang Rd, Hangzhou 310014, Zhejiang, Peoples R China.; Liu, FL (corresponding author), Zhejiang Univ, Affiliated Hosp 1, Dept Colorectal & Anal Surg, 79 Qingchun Rd, Hangzhou 310003, Zhejiang, Peoples R China. EM mouxz@zju.edu.cn; fanlong_liu@zju.edu.cn; cxiang@zju.edu.cn RI ; Zhenyu, Xu/AAW-7042-2020; li, yifei/IWU-7824-2023 OI Liu, Fanlong/0000-0002-3288-7262; Xu, Xiaogang/0000-0003-4364-5856 FU National Key R&D Program of China [2017YFA0105701]; National Science Foundation of China [81372463, 81672430, 81602706] FX This work was supported by the National Key R&D Program of China (no. 2017YFA0105701) and the National Science Foundation of China (no. 81372463, 81672430, and 81602706). We thank Xiaoqiang Mei, Rongrong Liu, Zhonghua Zeng, and Hangbin Hu for helping isolating issues from mice. In addition, we thank Editage for assistance with English language editing. 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PD JUL 1 PY 2019 VL 28 IS 13 BP 882 EP 896 DI 10.1089/scd.2018.0222 EA MAY 2019 PG 15 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA IG1OJ UT WOS:000469515000001 PM 30991894 DA 2025-10-02 ER PT J AU Babaei, A Baghi, HB Nezhadi, A Jamalpoor, Z AF Babaei, Abouzar Baghi, Hossein Bannazadeh Nezhadi, Akram Jamalpoor, Zahra TI In Vitro Anti-cancer Activity of Adipose-Derived Mesenchymal Stem Cells Increased after Infection with Oncolytic Reovirus SO ADVANCED PHARMACEUTICAL BULLETIN LA English DT Article DE Oncolytic virus; Reovirus type 3 Dearing; Mesenchymal stem cell; Glioblastoma cancer ID STROMAL CELLS; CANCER; VIRUSES; CARRIERS; THERAPY; CYTOTOXICITY; MIGRATION; PATHWAYS; REQUIRES AB Purpose: Reovirus type 3 Dearing (ReoT3D), a wild type oncolytic virus (OV) from the Reoviridae family, kills KRAS mutant cancer cells. However, the use of OVs has faced with some limitations such as immune responses, and delivery of OVs to the tumor sites in systemic therapy. To solve this, and also to increase the anti-cancer effects of these OVs, mesenchymal stem cells (MSCs) might be used as an effective vehicle for OVs delivery. In this study, we examined the anticancer effects of human adipose derived-MSCs (AD-MSCs) as a vehicle of ReoT3D against human glioblastoma cells. Methods: Here, AD-MSCs were characterized and toxicity of ReoT3D on them was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Then, capability of AD-MSCs for virus production was assessed by real-time polymerase chain reaction (PCR), and different in vitro anti-cancer experiments were applied for our anti-cancer purposes. Results: Our results from toxicity assay revealed that the isolated and provoked AD-MSCs were resistant to nontoxic concentration multiplicity of infection (MOI) >1 pfu/cells of ReoT3D. In addition, the results indicated that AD-MSCs were susceptible for virus life cycle complementation and were capable for production of virus progenies. Furthermore, our results showed that AD-MSCs had oncolysis effects and increased the anti-cancer effects of ReoT3D. Conclusion: AD-MSCs as a susceptible host for oncolytic reovirus could increase the anti-cancer activity of this OV against glioblastoma multiforme (GBM) cell line. C1 [Babaei, Abouzar; Jamalpoor, Zahra] Aja Univ Med Sci, Trauma Res Ctr, Tehran, Iran. [Baghi, Hossein Bannazadeh] Tabriz Univ Med Sci, Infect & Trop Dis Res Ctr, Tabriz, Iran. [Baghi, Hossein Bannazadeh] Tabriz Univ Med Sci, Immunol Res Ctr, Tabriz, Iran. [Nezhadi, Akram] Aja Univ Med Sci, Neurosci Res Ctr, Tehran, Iran. C3 Tabriz University of Medical Science; Tabriz University of Medical Science RP Jamalpoor, Z (corresponding author), Aja Univ Med Sci, Trauma Res Ctr, Tehran, Iran. EM z.jamalpoor@ajaums.ac.ir RI ; Bannazadeh Baghi, Hossein/N-3556-2018; jamalpoor, zahra/HGE-2127-2022 OI babaei, abouzar/0000-0002-1680-5730; Bannazadeh Baghi, Hossein/0000-0002-2513-5361; Nezhadi, Akram/0000-0002-3821-9441; FU Aja University of Medical Sciences [97000676] FX We thank Aja University of Medical Sciences for financial supports [grant number: 97000676]. 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Pharm. Bull. PY 2021 VL 11 IS 2 BP 361 EP 370 DI 10.34172/apb.2021.034 PG 10 WC Pharmacology & Pharmacy WE Emerging Sources Citation Index (ESCI) SC Pharmacology & Pharmacy GA QQ2AP UT WOS:000624328300019 PM 33880359 OA Green Submitted, gold DA 2025-10-02 ER PT J AU Xia, X Ji, T Chen, PB Li, X Fang, Y Gao, QL Liao, SJ You, LY Xu, HB Ma, QF Wu, P Hu, WC Wu, MF Cao, L Li, KZ Weng, YJ Han, ZQ Wei, JC Liu, RH Wang, SX Xu, G Wang, DW Zhou, JF Ma, D AF Xia, Xi Ji, Teng Chen, Pingbo Li, Xiao Fang, Yong Gao, Qinglei Liao, Shujie You, Lanying Xu, Hongbin Ma, Quanfu Wu, Peng Hu, Wencheng Wu, Mingfu Cao, Li Li, Kezhen Weng, Yanjie Han, Zhiqiang Wei, Junchen Liu, Ronghua Wang, Shixuan Xu, Gang Wang, Daowen Zhou, Jianfeng Ma, Ding TI Mesenchymal stem cells as carriers and amplifiers in CRAd delivery to tumors SO MOLECULAR CANCER LA English DT Article DE Mesenchymal Stem Cell; Conditionally Replicative Adenovirus; Cell Carrier; Signal Transducer and Activator of Transcription 3 (Stat3); Breast cancer ID ONCOLYTIC ADENOVIRUS; BREAST-CANCER; MELANOMA-CELLS; POTENT; PROGRESSION; GLIOMA; BIODISTRIBUTION; TRANSDUCTION; MIGRATION; PROGNOSIS AB Background: Mesenchymal stem cells (MSCs) have been considered to be the attractive vehicles for delivering therapeutic agents toward various tumor diseases. This study was to explore the distribution pattern, kinetic delivery of adenovirus, and therapeutic efficacy of the MSC loading of E1A mutant conditionally replicative adenovirus Adv-Stat3(-) which selectively replicated and expressed high levels of anti-sense Stat3 complementary DNA in breast cancer and melanoma cells. Methods: We assessed the release ability of conditionally replicative adenovirus (CRAd) from MSC using crystal violet staining, TCID50 assay, and quantitative PCR. In vitro killing competence of MSCs carrying Adv-Stat3(-) toward breast cancer and melanoma was performed using co-culture system of transwell plates. We examined tumor tropism of MSC by Prussian blue staining and immunofluorescence. In vivo killing competence of MSCs carrying Adv-Stat3(-) toward breast tumor was analyzed by comparison of tumor volumes and survival periods. Results: Adv-Stat3(-) amplified in MSCs and were released 4 days after infection. MSCs carrying Adv-Stat3(-) caused viral amplification, depletion of Stat3 and its downstream proteins, and led to significant apoptosis in breast cancer and melanoma cell lines. In vivo experiments confirmed the preferential localization of MSCs in the tumor periphery 24 hours after tail vein injection, and this localization was mainly detected in the tumor parenchyma after 72 hours. Intravenous injection of MSCs carrying Adv-Stat3(-) suppressed the Stat3 pathway, down-regulated Ki67 expression, and recruited CD11b-positive cells in the local tumor, inhibiting tumor growth and increasing the survival of tumor-bearing mice. Conclusions: These results indicate that MSCs migrate to the tumor site in a time-dependent manner and could be an effective platform for the targeted delivery of CRAd and the amplification of tumor killing effects. C1 [Xia, Xi; Ji, Teng; Chen, Pingbo; Li, Xiao; Fang, Yong; Gao, Qinglei; Liao, Shujie; Xu, Hongbin; Ma, Quanfu; Wu, Peng; Hu, Wencheng; Wu, Mingfu; Cao, Li; Li, Kezhen; Weng, Yanjie; Han, Zhiqiang; Wei, Junchen; Liu, Ronghua; Wang, Shixuan; Xu, Gang; Wang, Daowen; Zhou, Jianfeng; Ma, Ding] Huazhong Univ Sci & Technol, Canc Biol Res Ctr, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Hubei, Peoples R China. [Xia, Xi] Guangdong Med Coll, Affiliated Shenzhen Nanshan Hosp, Dept Gynecol & Obstet, Shenzhen 518052, Guangdong, Peoples R China. [Li, Xiao] So Med Univ, Dept Pediat, Maternal & Child Hlth Hosp Shenzhen, Shenzhen 518038, Guangdong, Peoples R China. [You, Lanying] Canc Hosp Fujian, Fujian Med Coll, Dept Gynecol, Fuzhou 350014, Fujian, Peoples R China. [Xu, Hongbin] Peoples Hosp Shenzhen, Dept Gynecol & Obstet, Shenzhen 518020, Guangdong, Peoples R China. C3 Huazhong University of Science & Technology; Guangdong Medical University; Southern Medical University - China RP Zhou, JF (corresponding author), Huazhong Univ Sci & Technol, Canc Biol Res Ctr, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Hubei, Peoples R China. EM jfzhou@tjh.tjmu.edu.cn; dma@tjh.tjmu.edu.cn RI HAN, ZHIQIANG/KWU-4849-2024; Xu, Gang/HNI-9325-2023; xiao, li/LRV-1500-2024; Gao, Qinglei/B-1141-2019; Zhou, Jianfeng/B-4888-2011; fang, yongkang/HKW-0054-2023; wang, xia/JFA-6314-2023; wu, peng/M-1812-2019; wang, wang/GWQ-7272-2022; Wang, Xiaogang/B-2439-2013 OI Wang, Xiaogang/0000-0002-7929-5889 FU National Science Foundation [81101971, 81101962, 81072135, 81001151, 30901586]; "973" Program of China [2009CB521800]; Guangdong Natural Science Foundation [B2011295, S2011040006012]; Shenzhen Scientific Program [20110422597, 201002006]; Nanshan Scientific Program [2010028] FX This work was supported by the National Science Foundation (No. 81101971; No. 81101962; No. 81072135; No. 81001151; No. 30901586; No. 81072135), "973" Program of China (No. 2009CB521800), Guangdong Natural Science Foundation (No. B2011295, No. S2011040006012), Shenzhen Scientific Program (No. 20110422597, No. 201002006) and Nanshan Scientific Program (No. 2010028). We are grateful to Huang Xiaoyuan and Cao Yang for their experiment suggestions. We also thank Ao Qilin for technical support in pathology. The authors indicate no potential conflict of interest or financial dependence regarding this publication. 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Cancer PD NOV 3 PY 2011 VL 10 AR 134 DI 10.1186/1476-4598-10-134 PG 12 WC Biochemistry & Molecular Biology; Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Oncology GA 849DB UT WOS:000297104600001 PM 22054049 OA gold, Green Published DA 2025-10-02 ER PT J AU Ahmed, AU Tyler, MA Thaci, B Alexiades, NG Han, Y Ulasov, IV Lesniak, MS AF Ahmed, Atique U. Tyler, Matthew A. Thaci, Bart Alexiades, Nikita G. Han, Yu Ulasov, Ilya V. Lesniak, Maciej S. TI A Comparative Study of Neural and Mesenchymal Stem Cell-Based Carriers for Oncolytic Adenovirus in a Model of Malignant Glioma SO MOLECULAR PHARMACEUTICS LA English DT Article DE stem cell; mesenchymal stem cell; neural stem cell; oncolytic adenovirus; glioblastoma; cell carrier; virotherapy ID GENE-THERAPY; INTRACRANIAL GLIOMA; MULTIPLE-SCLEROSIS; PROGENITOR CELLS; PRECURSOR CELLS; CANCER-THERAPY; OVARIAN-CANCER; IN-VITRO; BRAIN; MIGRATION AB Glioblastoma multiform e is a primary malignancy of the central nervous system that is universally fatal due to its disseminated nature. Recent investigations have focused on the unique tumor-tropic properties of stem cells as a novel platform for targeted delivery of anticancer agents to the brain. Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) both have the potential to function as cell carriers for targeted delivery of a glioma restricted oncolytic virus to disseminated tumor due to their reported tumor tropism. In this study, we evaluated NSCs and MSCs as cellular delivery vehicles for an oncolytic adenovirus in the context of human glioma. We report the first preclinical comparison of the two cell lines and show that, while both stem cell lines are able to support therapeutic adenoviral replication intracellularly, the amount of virus released from NSCs was a log higher than the MSC (p < 0.001). Moreover, only virus loaded NSCs that were administered intracranially in an orthotopic glioma model significantly prolonged the survival of tumor bearing animals (median survival for NSCs 68.5 days vs 44 days for MSCs, p < 0.002). Loading oncolytic adenovirus into NSCs and MSCs also led to expression of both pro- and anti-inflammatory genes and decreased vector-mediated neuroinflammation. Our results indicate that, despite possessing a comparable migratory capacity, NSCs display superior therapeutic efficacy in the context of intracranial tumors. Taken together, these findings argue in favor of NSCs as an effective cell carrier for antiglioma oncolytic virotherapy. C1 [Lesniak, Maciej S.] Univ Chicago, Brain Tumor Ctr, Pritzker Sch Med, Chicago, IL 60637 USA. C3 University of Chicago RP Lesniak, MS (corresponding author), Univ Chicago, Brain Tumor Ctr, Pritzker Sch Med, 5841 S Maryland Ave,MC 3026, Chicago, IL 60637 USA. EM mlesniak@surgery.bsd.uchicago.edu RI ; Ulasov, Ilya/A-2352-2014; Ahmed, Atique/HNS-0597-2023; Alexiades, Nikita/KLE-0924-2024; Yu, Jinghua/L-3794-2017 OI Ahmed, Atique/0000-0003-4795-0188; Ulasov, Ilya/0000-0002-0818-0363; Thaci, Bart/0000-0001-5392-7174 FU NCI [R01CA122930, R01CA138587]; National Institute of Neurological Disorders and Stroke [U01NS069997]; American Cancer Society [RSG-07-276-01-MGO]; University of Chicago FX We would like to thank Simona M. Ahmed for editing the manuscript, Dingcai Cao and Feifei Liu for statistical analysis. This research was supported by the NCI (R01CA122930, R01CA138587), the National Institute of Neurological Disorders and Stroke (U01NS069997), the American Cancer Society (RSG-07-276-01-MGO) and University of Chicago BSD IRI Pilot Grant. 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PD SEP-OCT PY 2011 VL 8 IS 5 BP 1559 EP 1572 DI 10.1021/mp200161f PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 826IJ UT WOS:000295347500013 PM 21718006 DA 2025-10-02 ER PT J AU Wang, XY Yang, YC Wang, NX Wu, XJ Xu, JW Zhou, YH Zhao, X He, ZX AF Wang, Xianyao Yang, Yichen Wang, Nianxue Wu, Xijun Xu, Jianwei Zhou, Yanhua Zhao, Xing He, Zhixu TI Mesenchymal stem cell carriers enhance antitumor efficacy induced by oncolytic reovirus in acute myeloid leukemia SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Human umbilical cord mesenchymal stem cells; Oncolytic reovirus; Acute myeloid leukemia; Antitumor efficacy; CXCL10; Virotherapy ID PHASE-I TRIAL; STROMAL CELLS; BONE-MARROW; PROLIFERATION; MIGRATION; REOLYSIN; THERAPY; UPDATE; TISSUE; VIRUS AB Chemotherapy is the main treatment for acute myeloid leukemia (AML), but the therapeutic efficacy is modest, and most commonly manifests as relapse from remission. Thus, improving long-term AML survival is a crucial clinical challenge. In recent years, oncolytic virotherapy has provided an alternative approach for AML treatment. The use of oncolytic reoviruses has been explored in more than 30 clinical trials for safety and feasibility issues. However, like other oncolytic viruses, neutralizing antibodies (NAbs) reduce therapeutic efficacy. To tackle this problem, human umbilical cord mesenchymal stem cells (hUC-MSCs) were used to deliver reovirus using in vitro and in vivo models. Human UC-MSCs were successfully loaded with reovirus, without impairing biological function. We also observed in vitro protective effects of hUC-MSCs on reovirus in the presence of NAbs. In the immunocompromised AML mouse model, hUC-MSCs effectively carried reoviruses to tumor lesions and significantly prolonged the survival of AML xenografts in mice in the presence of a high titer anti-reovirus antibody (p = 0.001). However, reovirus-induced activation of AKT, stress-activated protein kinase/c-Jun Nterminal kinase (SAPK/JNK), and NF-?B signaling led to the maintenance of intrinsic migratory properties and secretion of pro-inflammatory cytokines from hUC-MSCs, particularly CXCL10. In immuno-competent AML mice, MSCs carrying reovirus triggered immune responses, and eventually inhibited tumor growth. Therefore, these results suggest that MSCs as carriers of oncolytic reoviruses can enhance the antitumor efficacy of virotherapy. C1 [Wang, Xianyao; Wang, Nianxue; Zhao, Xing; He, Zhixu] Guizhou Med Univ, Coll Basic Med Sci, Dept Immunol, Guiyang 550025, Guizhou, Peoples R China. [Wang, Xianyao; Yang, Yichen; Wang, Nianxue; Wu, Xijun; Xu, Jianwei; Zhou, Yanhua; Zhao, Xing] Guizhou Med Univ, Ctr Tissue Engn & Stem Cell Res, Guiyang 550004, Peoples R China. [Wang, Xianyao; Wu, Xijun; Xu, Jianwei; Zhou, Yanhua; Zhao, Xing; He, Zhixu] Chinese Acad Med Sci, Key Lab Adult Stem Cell Translat Res, Guiyang 550004, Peoples R China. [Xu, Jianwei] Guizhou Med Univ, Dept Pharmacol, Guiyang 550025, Peoples R China. [He, Zhixu] Zunyi Med Univ, Affiliated Hosp, Dept Pediat, Zunyi 563000, Guizhou, Peoples R China. C3 Guizhou Medical University; Guizhou Medical University; Chinese Academy of Medical Sciences - Peking Union Medical College; Guizhou Medical University; Zunyi Medical University RP Zhao, X; He, ZX (corresponding author), Guizhou Med Univ, Coll Basic Med Sci, Dept Immunol, Guiyang 550025, Guizhou, Peoples R China. EM xingzhao@gmc.edu.cn; hzx@gmc.edu.cn RI Wang, Xianyao/LUY-2454-2024; Xu, Jian-wei/ABI-7923-2020; he, zeying/HCH-3380-2022 OI Wang, Xianyao/0000-0002-1742-2045; FU National Natural Science Foundation of China [81871313, 81860542]; Key Projects of Guizhou Provincial Department of Science and Technology [Qian Ke He Zhi Cheng (2020) 4Y192]; Graduate Student Innovation Program in Guizhou Province [Qian Jiao He YJSCXJH (2020) 143]; Guizhou Provincial Natural Science Foundation [(2019)5663]; Program for Top Scientific and Technological Talents in Guizhou Province [KY (2018)049]; Guizhou Province Science and Technology Talent Platform Project [(2019)5406]; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2018PT31048, 2019PT310013] FX This work was supported by the National Natural Science Foundation of China (grant numbers 81871313, 81860542); Key Projects of Guizhou Provincial Department of Science and Technology [grant number Qian Ke He Zhi Cheng (2020) 4Y192]; the Graduate Student Innovation Program in Guizhou Province [grant number Qian Jiao He YJSCXJH (2020) 143]; the Guizhou Provincial Natural Science Foundation [grant number (2019)5663]; the Program for Top Scientific and Technological Talents in Guizhou Province [grant number KY (2018)049]; the Guizhou Province Science and Technology Talent Platform Project [grant number (2019)5406]; and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (grant numbers 2018PT31048, 2019PT310013). 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Immunopharmacol. PD MAY PY 2021 VL 94 AR 107437 DI 10.1016/j.intimp.2021.107437 EA FEB 2021 PG 13 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA RX7SO UT WOS:000647419900002 PM 33571747 DA 2025-10-02 ER PT J AU Wu, YY Liu, Q Xiang, W Fu, P AF Wu, Yuyi Liu, Qiang Xiang, Wei Fu, Peng TI The immunosuppressive microenvironment modulated by glioma-associated mesenchymal stem cells: Current status and potential strategies SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE Glioma; Glioma-associated mesenchymal stem cells; Immunosuppressive microenvironment; Tumor-stroma interactions; Therapeutic strategies ID ONCOLYTIC ADENOVIRUS; STROMAL CELLS; GENE-THERAPY; T-CELLS; TUMOR; CANCER; DIFFERENTIATION; GLIOBLASTOMA; IDENTIFICATION; PROLIFERATION AB Glioma, the most prevalent primary malignant tumor of the central nervous system, exhibits aggressive progression and poor prognosis, largely due to its highly immunosuppressive tumor microenvironment (TME). Glioma-associated mesenchymal stem cells (GA-MSCs), a key component of the glioma TME, play a dual and context-dependent role in tumor biology. On one hand, GA-MSCs actively shape immunosuppression by interacting with various immune cells-including T cells, B cells, natural killer (NK) cells, dendritic cells (DCs), and macrophages-via soluble factors (e.g., TGF-beta, PGE2, miR-21) and cell-contact mechanisms, thereby facilitating tumor immune evasion. They also promote glioma progression by enhancing the stemness, invasiveness, and chemoresistance of glioma stem cells (GSCs) through pathways such as IL-6/STAT3 and mitochondrial transfer, while contributing to pathological angiogenesis via differentiation into pericytes and secretion of pro-angiogenic factors like VEGF. On the other hand, GA-MSCs possess therapeutic potential: genetically engineered GA-MSCs can secrete pro-inflammatory cytokines (e.g., IL-12, IFN-beta) or immune checkpoint blockers (e.g., scFv-PD1) to reverse immunosuppression, serve as carriers for targeted delivery of chemotherapeutics, miRNAs, suicide genes, or oncolytic viruses, and enhance anti-tumor immune responses. However, clinical translation is hindered by challenges including residual immunosuppressive activity, unstable transgene expression, limited migration efficiency, and safety concerns. This review summarizes the complex mechanisms by which GA-MSCs modulate the glioma TME, highlights their bidirectional roles in tumor progression and immunotherapy, and discusses potential strategies to overcome current limitations, aiming to provide insights for developing novel therapies targeting GA-MSCs and their interactions within the glioma microenvironment. C1 [Wu, Yuyi; Liu, Qiang; Xiang, Wei; Fu, Peng] Huazhong Univ Sci & Technol, Wuhan Union Hosp, Dept Neurosurg, Wuhan, Peoples R China. C3 Huazhong University of Science & Technology RP Xiang, W; Fu, P (corresponding author), Huazhong Univ Sci & Technol, Wuhan Union Hosp, Dept Neurosurg, Wuhan, Peoples R China. EM xiangwei20@hotmail.com; pfu@hust.edu.cn FU National Natural Science Foundation of China [82472953, 82272884] FX This work was supported by the National Natural Science Foundation of China (82472953 and 82272884) . 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Biophys. Acta-Rev. Cancer PD OCT PY 2025 VL 1880 IS 5 AR 189410 DI 10.1016/j.bbcan.2025.189410 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 6OS0S UT WOS:001558382200001 PM 40780462 DA 2025-10-02 ER PT J AU Gómez, A Sardón, D Cejalvo, T Vázquez, F García-Castro, J Perisé-Barrios, AJ AF Gomez, Ana Sardon, David Cejalvo, Teresa Vazquez, Fernando Garcia-Castro, Javier Judith Perise-Barrios, Ana TI Biodistribution Analysis of Oncolytic Adenoviruses in Canine Patient Necropsy Samples Treated with Cellular Virotherapy SO MOLECULAR THERAPY-ONCOLYTICS LA English DT Article ID MESENCHYMAL STEM-CELLS; NEUROBLASTOMA; TUMORS AB Oncolytic immunotherapy with competent viruses is an emerging approach in cancer treatment. The clinical safety of many types of oncolytic viruses (OVs) has been demonstrated. However, there is a lack of information about viral biodistribution in patients. The available data about oncolytic adenovirus biodistribution in human subjects treated intravenously consists of virus detection in body fluids, a few tumor biopsies, and a single report of patient necropsy samples. There is no information about adenoviral biodistribution in patients treated intravenously with cellular vehicles carrying an oncolytic adenovirus. We previously published reports regarding the efficacy and clinical safety of infusing mesenchymal stem cells (MSCs) infected with an OV in human and canine patients. In this study, we performed necropsies on 12 canine patients treated with dCelyvir, canine MSCs infected with ICOCAV17, a canine oncolytic adenovirus. The prevalence of microscopic lesions, especially chronic inflammatory responses in different organs, was higher than expected. Concomitantly, we found a positive immunoreaction to ICOCAV17 in analyzed samples. These findings support a possible role of the virus in development of histopathological alterations and ongoing systemic viral replication of ICOCAV17 in the period after therapy administration. C1 [Gomez, Ana; Sardon, David; Vazquez, Fernando] Univ Alfonso X Sabio, Vet Pathol Unit, Madrid 28691, Spain. [Cejalvo, Teresa; Garcia-Castro, Javier; Judith Perise-Barrios, Ana] Inst Salud Carlos III, Cellular Biotechnol Unit, Madrid 28220, Spain. [Garcia-Castro, Javier; Judith Perise-Barrios, Ana] Univ Alfonso X Sabio, Biomed Res Unit, Madrid 28691, Spain. C3 Universidad Alfonso X el Sabio (UAX); Instituto de Salud Carlos III; Universidad Alfonso X el Sabio (UAX) RP Perisé-Barrios, AJ (corresponding author), Univ Alfonso X Sabio, Biomed Res Unit, Madrid 28691, Spain. EM aperibar@uax.es RI Garcia-Castro, Javier/ABC-9741-2021; Perisé Barrios, Ana Judith/A-4007-2019; Garcia-Castro, Javier/H-5274-2011 OI Garcia-Castro, Javier/0000-0001-7604-1640; Gomez Vitores, Ana/0000-0003-4975-0171; Perise Barrios, Ana Judith/0000-0002-0136-3968; Cejalvo, Teresa/0000-0002-4304-2150 FU Fundacion Universidad Alfonso X el Sabio, Madrid, Spain [1.010.909]; Instituto de Salud Carlos III, Spain [PI14CIII/00005, PI17CIII/00013]; Consejeria de Educacion, Juventud y Deporte, Comunidad de Madrid, Spain [P2017/BMD-3692]; Fundacion Oncohematologia Infantil; AFANION; Asociacion Pablo Ugarte FX The authors would like to thank Paloma Rey Porto for technical support. ICOCAV17 was kindly provided by Dr. Ramon Alemany Bonastre (IDIBELL-Institut Catala d'Oncologia, l'Hospitalet de Llobregat). This study was funded by Fundacion Universidad Alfonso X el Sabio, Madrid, Spain (1.010.909 to A.J.P.-B.); Instituto de Salud Carlos III, Spain (PI14CIII/00005 and PI17CIII/00013 to J.G.-C.); Consejeria de Educacion, Juventud y Deporte, Comunidad de Madrid, Spain (P2017/BMD-3692 to J.G.-C.); Fundacion Oncohematologia Infantil; AFANION; and Asociacion Pablo Ugarte, whose support we gratefully acknowledge. The graphical abstract was created with BioRender. 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Ther.-Oncolytics PD SEP 25 PY 2020 VL 18 BP 525 EP 534 DI 10.1016/j.omto.2020.08.006 PG 10 WC Oncology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Research & Experimental Medicine GA NW7AL UT WOS:000575168700043 PM 32995478 OA gold, Green Submitted DA 2025-10-02 ER PT J AU Hsiao, WC Sung, SY Liao, CH Wu, HC Hsieh, CL AF Hsiao, Wan-Chi Sung, Shian-Ying Liao, Chia-Hui Wu, Hsi-Chin Hsieh, Chia-Ling TI Vitamin D3-Inducible Mesenchymal Stem Cell-Based Delivery of Conditionally Replicating Adenoviruses Effectively Targets Renal Cell Carcinoma and Inhibits Tumor Growth SO MOLECULAR PHARMACEUTICS LA English DT Article DE bone marrow-derived mesenchymal stem cells; inducible cell-based gene delivery; human osteocalcin promoter; vitamin D-3; renal cell carcinoma ID HUMAN PROSTATE-CANCER; HUMAN OSTEOCALCIN PROMOTER; MARROW STROMAL CELLS; I/II CLINICAL-TRIAL; GENE-THERAPY; ONCOLYTIC ADENOVIRUS; BONE METASTASIS; MODEL; COMPETENT; VEHICLES AB Cell-based carriers were recently exploited as a tumor-targeting tool to improve systemic delivery of oncolytic viruses for cancer therapy. However, the slow clearance of carrier cells from normal organs indicates the need for a controllable system which allows viral delivery only when the carrier cells reach the tumor site. In this study, we sought to develop a pharmaceutically inducible cell-based oncolytic adenovirus delivery strategy for effective targeting and treatment of renal cell carcinoma (RCC), which is one of the most malignant tumor types with an unfavorable prognosis. Herein, we demonstrated the intrinsic tumor homing property of human bone marrow-derived mesenchymal stem cells (hMSCs) to specifically localize primary and metastatic RCC tumors after systemic administration in a clinically relevant orthotopic animal model. The platelet derived growth factor AA (PDGF-AA) secreted from RCC was identified as a chemoattractant responsible for the recruitment of hMSCs. Like endogenous osteocalcin whose barely detectable level of expression was dramatically induced by vitamin D-3, the silenced replication of human osteocalcin promoter-directed Ad-hOC-E1 oncolytic adenoviruses loaded in hMSCs was rapidly activated, and the released oncolytic adenoviruses sequentially killed cocultured RCC cells upon vitamin D-3 exposure. Moreover, the systemic treatment of RCC tumor-bearing mice with hMSC cell carriers loaded with Ad-hOC-E1 had very limited effects on tumor growth, but the loaded hMSCs combined with vitamin D-3 treatment induced effective viral delivery to RCC tumors and significant tumor regression. Therapeutic effects of hMSC-based Ad-hOC-E1 delivery were confirmed to be significantly greater than those of injection of carrier-free Ad-hOC-E1. Our results presented the first preclinical demonstration of a novel controllable cell-based gene delivery strategy that combines the advantages of tumor tropism and vitamin D-3-regulatable human osteocalcin promoter-directed gene expression of hMSCs to improve oncolytic virotherapy for advanced RCC. C1 [Sung, Shian-Ying; Liao, Chia-Hui; Hsieh, Chia-Ling] China Med Univ Hosp, Ctr Mol Med, Taichung 40454, Taiwan. [Hsiao, Wan-Chi; Sung, Shian-Ying; Hsieh, Chia-Ling] China Med Univ, Grad Inst Canc Biol, Taichung 40447, Taiwan. [Wu, Hsi-Chin] China Med Univ, Sch Med, Taichung 40447, Taiwan. [Wu, Hsi-Chin] China Med Univ Hosp, Dept Urol, Taichung 40447, Taiwan. [Hsieh, Chia-Ling] Asia Univ, Dept Biotechnol, Taichung, Taiwan. C3 China Medical University Taiwan; China Medical University Hospital - Taiwan; China Medical University Taiwan; China Medical University Taiwan; China Medical University Taiwan; China Medical University Hospital - Taiwan; Asia University Taiwan RP Hsieh, CL (corresponding author), China Med Univ Hosp, Ctr Mol Med, 9F 6,Hsueh Shih Rd, Taichung 40454, Taiwan. EM chsieh2@mail.cmu.edu.tw RI WU, HSI-CHIN/A-2306-2013 FU National Science Council (NSC) [100-3122-B-039-005, 99-2320-B-039-029-MY3, 99-2632-B-039-001-MY3]; National Health Research Institutes in Taiwan [NHRI EX-100-9902BI] FX We thank MedcomAsia for their editorial assistance. This work was supported by NSC 100-3122-B-039-005, NSC 99-2320-B-039-029-MY3, and NSC 99-2632-B-039-001-MY3 from the National Science Council and NHRI EX-100-9902BI from the National Health Research Institutes in Taiwan. 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PD MAY PY 2012 VL 9 IS 5 BP 1396 EP 1408 DI 10.1021/mp200649g PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 941KC UT WOS:000303961100034 PM 22480282 DA 2025-10-02 ER PT J AU Otero, JG Alcami, AAA Belmonte-Beitia, J AF Otero, Jose Garcia Alcami, Arturo Alvarez-Arenas Belmonte-Beitia, Juan TI Dynamics and analysis of a mathematical model of neuroblastoma treated with Celyvir SO APPLIED MATHEMATICAL MODELLING LA English DT Article DE Impulsive differential equations; Neuroblastoma; Limit cycle; Oncolytic virus; Stability ID MESENCHYMAL STEM-CELLS; OF-THE-ART; ONCOLYTIC VIROTHERAPY; PARAMETER-ESTIMATION; IMMUNE-SYSTEM; DELIVERY; VEHICLES; CANCER; IMMUNOTHERAPY; RESISTANCE AB Celyvir viro-immunotherapy - a therapy using mesenchymal stem cells (MSCs) infected with the oncolytic adenovirus ICOVIR 5, an innovative oncolytic adenovirus - is a new therapeutic approach in cancer treatment. The purpose of this study is to create a mathematical model describing the relationships between immune, cancer and viral cells in pediatric patients with neuroblastoma. This was done by studying two different ways of applying the treatment: continuous and periodic therapy. Analysis of the first mathematical model identifies equilibrium points, their stability properties and bifurcation points. It can also identify bistability regimes in which therapy can induce either tumour-free equilibrium or tumour progression, depending only on the initial conditions. The second model reveals the existence of a threshold value of viral load, beyond which the patient's recovery could be assured. The models make it clear that both the intensity of the viral load and the time over which treatment is given must be sufficient to ensure the success of the therapy. Low levels of treatment may fail to eliminate neuroblastoma, while stopping therapy early could lead to recurrence. C1 [Otero, Jose Garcia; Alcami, Arturo Alvarez-Arenas; Belmonte-Beitia, Juan] Univ Castilla La Mancha, Dept Matemat, Math Oncol Lab, Ciudad Real 13071, Spain. C3 Universidad de Castilla-La Mancha RP Belmonte-Beitia, J (corresponding author), Univ Castilla La Mancha, Dept Matemat, Math Oncol Lab, Ciudad Real 13071, Spain. EM juan.belmonte@uclm.es RI Belmonte Beitia, Juan/S-4515-2017; Beitia, Juan/S-4515-2017; García, José/JQV-4041-2023 OI Belmonte Beitia, Juan/0000-0002-5003-1150; Garcia Otero, Jose/0009-0007-8092-5044; FU Junta de Comunidades de Castilla-La Mancha, Spain [SBPLY/19/180501/000211]; Ministerio de Ciencia e Innovaci?n, Spain [PID2019-110895RB-10 0, 2021-AYUDA-30849] FX Acknowledgements This research has been supported by a grant awarded to J.B.-B by the Junta de Comunidades de Castilla-La Mancha, Spain (grant number SBPLY/19/180501/000211) . This research has also been supported by the Ministerio de Ciencia e Innovaci?n, Spain (grant number PID2019-110895RB-10 0) . J.G.O wishes to thank the NeN Association for the financial support (Ref. 2021-AYUDA-30849) . 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Math. Model. PD OCT PY 2022 VL 110 BP 131 EP 148 DI 10.1016/j.apm.2022.05.038 EA JUN 2022 PG 18 WC Engineering, Multidisciplinary; Mathematics, Interdisciplinary Applications; Mechanics WE Science Citation Index Expanded (SCI-EXPANDED) SC Engineering; Mathematics; Mechanics GA 1Z1DU UT WOS:000808573500009 OA hybrid DA 2025-10-02 ER PT J AU Thorne, SH Contag, CH AF Thorne, S. H. Contag, C. H. TI Combining immune cell and viral therapy for the treatment of cancer SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE oncolytic virus; immunotherapy; cancer therapy; imaging ID MESENCHYMAL STEM-CELLS; T-CELLS; ONCOLYTIC VIROTHERAPY; SYSTEMIC DELIVERY; GENE-TRANSFER; KILLER-CELLS; ADENOVIRUS; LYMPHOMA; VECTORS; VIRUS AB A variety of viral-based and immune cell therapies have been proposed for use in the treatment of cancer. One possible approach to improve the effectiveness of these biological agents may be to combine them such that we can take advantage of natural immune cell-pathogen relationships. Here we discuss these potential approaches with particular emphasis on the use of immune cells as carrier vehicles to deliver viral therapies to the tumor. C1 Stanford Univ, BioX Program, Mol Imaging Program Stanford, Stanford, CA 94305 USA. Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. Stanford Univ, Dept Immunol, Stanford, CA 94305 USA. C3 Stanford University; Stanford University; Stanford University; Stanford University RP Thorne, SH (corresponding author), Stanford Univ, BioX Program, Mol Imaging Program Stanford, Stanford, CA 94305 USA. 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PD JUN PY 2007 VL 64 IS 12 BP 1449 EP 1451 DI 10.1007/s00018-007-6550-z PG 3 WC Biochemistry & Molecular Biology; Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Cell Biology GA 179EJ UT WOS:000247272100001 PM 17404689 OA Green Submitted DA 2025-10-02 ER PT J AU Yuan, XF Lu, Y Yang, YY Tian, WC Fan, DM Liu, RQ Lei, XM Xia, YF Yang, L Yan, S Xiong, DS AF Yuan, Xiangfei Lu, Yang Yang, Yuanyuan Tian, Wencong Fan, Dongmei Liu, Ruoqi Lei, Xiaomin Xia, Yafei Yang, Lei Yan, Shu Xiong, Dongsheng TI Systemic administration of mesenchymal stem cells loaded with a novel oncolytic adenovirus carrying a bispecific T cell engager against hepatocellular carcinoma SO ONCOIMMUNOLOGY LA English DT Article DE AFP; BiTE; Crad; HCC; hepatic differentiation; HUMSC; PBMC; PD-L1; tumor heterogeneity ID HEPATOCARCINOMA; EXPRESSION AB We previously established a hepatocellular carcinoma (HCC) targeting system of conditionally replicative adenovirus (CRAd) delivered by human umbilical cord-derived mesenchymal stem cells (HUMSCs). However, this system needed to be developed further to enhance the antitumor effect and overcome the limitations caused by the alpha-fetoprotein (AFP) heterogeneity of HCC. In this study, a bispecific T cell engager (BiTE) targeting programmed death ligand 1 controlled by the human telomerase reverse transcriptase promoter was armed on the CRAd of the old system. It was demonstrated on orthotopic transplantation model mice that the new system had a better anti-tumor effect with no more damage to extrahepatic organs and less liver injury, and the infiltration and activation of T cells were significantly enhanced in the tumor tissues of the model mice treated with the new system. Importantly, we confirmed that the new system eliminated the AFP-negative cells on AFP heterogeneous tumor models efficiently. Conclusion: Compared with the old system, the new system provided a more effective and safer strategy against HCC. C1 [Yuan, Xiangfei; Yang, Lei] Tianjin Med Univ NanKai Hosp, Tianjin Key Lab Acute Abdomen Dis Associated Organ, Tianjin, Peoples R China. [Lu, Yang; Fan, Dongmei; Liu, Ruoqi; Lei, Xiaomin; Xiong, Dongsheng] Chinese Acad Med Sci & Peking Union Med Coll, Inst Hematol & Blood Dis Hosp, Natl Clin Res Ctr Blood Dis, State Key Lab Expt Hematol,Haihe Lab Cell Ecosyst, Tianjin, Peoples R China. [Yang, Yuanyuan] Tianjin Med Univ, Dept Pharm, Gen Hosp, Tianjin, Peoples R China. [Tian, Wencong] Tianjin Union Med Ctr, Dept Gen Surg, Tianjin, Peoples R China. [Xia, Yafei; Yan, Shu] Tianjin Univ, Integrated Chinese & Western Med Hosp, Dept Pharm, Tianjin, Peoples R China. [Yuan, Xiangfei] Tianjin Med Univ, NanKai Hosp, Tianjin Key Lab Acute Abdomen Dis Associated Organ, 6, Changjiang Rd, Tianjin 300100, Peoples R China. [Yan, Shu] Tianjin Univ, Integrated Chinese & Western Med Hosp, Dept Pharm, 6, Changjiang Rd, Tianjin 300100, Peoples R China. [Xiong, Dongsheng] Chinese Acad Med Sci & Peking Union Med Coll, Inst Hematol & Blood Dis Hosp, Natl Clin Res Ctr Blood Dis, State Key Lab Expt Hematol,Haihe Lab Cell Ecosyst, 288 Nanjing Rd, Tianjin 300020, Peoples R China. C3 Tianjin Medical University; Chinese Academy of Medical Sciences - Peking Union Medical College; Institute of Hematology & Blood Diseases Hospital - CAMS; Peking Union Medical College; Tianjin Medical University; Tianjin University; Tianjin Medical University; Tianjin University; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Institute of Hematology & Blood Diseases Hospital - CAMS RP Yuan, XF (corresponding author), Tianjin Med Univ, NanKai Hosp, Tianjin Key Lab Acute Abdomen Dis Associated Organ, 6, Changjiang Rd, Tianjin 300100, Peoples R China.; Yan, S (corresponding author), Tianjin Univ, Integrated Chinese & Western Med Hosp, Dept Pharm, 6, Changjiang Rd, Tianjin 300100, Peoples R China.; Xiong, DS (corresponding author), Chinese Acad Med Sci & Peking Union Med Coll, Inst Hematol & Blood Dis Hosp, Natl Clin Res Ctr Blood Dis, State Key Lab Expt Hematol,Haihe Lab Cell Ecosyst, 288 Nanjing Rd, Tianjin 300020, Peoples R China. EM yuanxiangfei100@163.com; 13389989966@163.com; dsxiong@ihcams.ac.cn RI Yang, Yuanyuan/HLH-7749-2023; fan, dongmei/MVU-0145-2025 FU Tianjin Municipal Science and Technology Commission Grant [19JCZDJC33100]; National Natural Science Foundation of China [82003266, 81830005]; CAMS Innovation Fund for Medical Sciences [2021-I2M-1-041]; Haihe Laboratory of Cell Ecosystem Innovation Fund [HH22KYZX0032]; Scientific Foundation of Tianjin Municipal Education Commission [2019KJ196] FX This study was supported by the Tianjin Municipal Science and Technology Commission Grant (Grant No. 19JCZDJC33100); the National Natural Science Foundation of China (Grant Nos . 82003266 and 81830005); CAMS Innovation Fund for Medical Sciences (Grant No. 2021-I2M-1-041); Haihe Laboratory of Cell Ecosystem Innovation Fund (Grant No. HH22KYZX0032); Scientific Foundation of Tianjin Municipal Education Commission (Grant No. 2019KJ196). 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This issue can be overcome by using mesenchymal stem cells (MSCs) as carrier cells for oncolytic viruses (OVs). However, it remains elusive whether MSC source influences the antitumor effect. Here, we demonstrate that their source affects the migration ability and oncolytic activity of OV-loaded MSCs. Among human MSCs derived from different tissues, bone marrow-derived MSCs (BMMSCs) showed a high migration ability toward cancer cells in two- and three-dimensional MSC-cancer cell co-culture models. Comprehensive gene expression and Gene Ontology-based functional analyses suggested that genes involved in cell migration and cytokine response influence the cancer-specific tropism of BMMSCs. Furthermore, MSC origin affected the susceptibility to OVs, including cytotoxicity resistance and OV release from MSCs. MSC-mediated OV delivery signifi- cantly increased the viral spread and antitumor activity compared with delivery by OVs alone, and OV-loaded BMMSCs demonstrated the most potent antitumor effect among OV-loaded MSCs. Our results offer promising insights into cancer gene therapy with carrier cells and can help with the selection of an appropriate MSC source for MSC-based OV therapy. C1 [Sukegawa, Makoto; Miyagawa, Yoshitaka; Kuroda, Seiji; Yamazaki, Yoshiyuki; Yamamoto, Motoko; Adachi, Kumi; Sato, Hirofumi; Sato, Yuriko; Sakai, Mashito] Nippon Med Sch, Grad Sch Med, Dept Biochem & Mol Biol, 1-1-5 Sendagi,Bunkyo ku, Tokyo 1138602, Japan. [Sukegawa, Makoto; Taniai, Nobuhiko] Nippon Med Sch, Grad Sch Med, Dept Gastrointestinal Surg, Musashikosugi Hosp, Kawasaki, Japan. [Sukegawa, Makoto; Yoshida, Hiroshi] Nippon Med Sch, Grad Sch Med, Dept Surg, Tokyo, Japan. [Umezawa, Akihiro] Natl Ctr Child Hlth & Dev, Res Inst, Ctr Regenerat Med, Tokyo, Japan. [Okada, Takashi] Univ Tokyo, Inst Med Sci, Div Mol & Med Genet, Tokyo, Japan. C3 Nippon Medical School; Nippon Medical School; Nippon Medical School; National Center for Child Health & Development - Japan; University of Tokyo RP Miyagawa, Y; Sakai, M (corresponding author), Nippon Med Sch, Grad Sch Med, Dept Biochem & Mol Biol, 1-1-5 Sendagi,Bunkyo ku, Tokyo 1138602, Japan. EM yoshitaka-miyagawa@nms.ac.jp; m-sakai@nms.ac.jp FU Japan Society for the Promotion of Science [21H03828]; Vehicle Racing Commemorative Foundation [6225] FX We are grateful to Takenori Fujii (Nippon Medical School) for pathological analysis, Masumi Shimizu (Nippon Medical School) for FACS analysis, Takeshi Kijima (Yokohama General Hospital) for advice on 3D culture, and Yuka Ohyama and Izumi Yoshida (Nippon Medical School) for cell culture. We thank Takara Bio Inc. for providing C-REV. This research was supported by Japan Society for the Promotion of Science (21H03828) and Vehicle Racing Commemorative Foundation (6225) . 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PD DEC 19 PY 2024 VL 32 IS 4 AR 200896 DI 10.1016/j.omton.2024.200896 EA NOV 2024 PG 17 WC Oncology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Research & Experimental Medicine GA L4K3P UT WOS:001350419800001 PM 39554905 OA gold, Green Submitted DA 2025-10-02 ER PT J AU Yang, ML Hu, CY Lee, YC Chang, CC Chen, YC Lee, PR Su, BH Chen, PC Shiau, AL Shieh, GS Wu, CL Wu, P AF Yang, Mei-Lin Hu, Che-Yuan Lee, Ya-Che Chang, Chao-Ching Chen, Yi-Cheng Lee, Pei-Ru Su, Bing-Hua Chen, Pi-Che Shiau, Ai-Li Shieh, Gia-Shing Wu, Chao-Liang Wu, Pensee TI Syngeneic mesenchymal stem cells loaded with telomerase-dependent oncolytic adenoviruses enhance anti-metastatic efficacy SO STEM CELLS TRANSLATIONAL MEDICINE LA English DT Article DE oncolytic adenovirus; mesenchymal stem cell; telomerase; TERT; tumor microenvironment; metastasis; bladder cancer; SDF-1 ID TERT PROMOTER MUTATIONS; E1B-DELETED ADENOVIRUS; GENE-THERAPY; CANCER; EXPRESSION; REPLICATION; INFLAMMATION; MIGRATION AB Oncolytic adenoviruses have emerged as a promising therapeutic approach for cancer therapy. However, systemic delivery of the viruses to metastatic tumors remains a major challenge. Mesenchymal stem cells (MSCs) possess tumor tropism property and can be used as cellular vehicles for delivering oncolytic adenoviruses to tumor sites. Since telomerase activity is found in similar to 90% of human carcinomas, but undetected in normal adult cells, the human telomerase reverse transcriptase gene (TERT) promoter can be exploited for regulating the replication of oncolytic adenoviruses. Here, we evaluated the antitumor effects of syngeneic murine MSCs loaded with the luciferase-expressing, telomerase-dependent oncolytic adenovirus Ad.GS2 (MSC-Ad.GS2) and Ad.GS2 alone on metastatic MBT-2 bladder tumors. MSCs supported a low degree of Ad.GS2 replication, which could be augmented by coculture with MBT-2 cells or tumor-conditioned medium (TCM), suggesting that viral replication is increased when MSC-Ad.GS2 migrates to tumor sites. MBT-2 cells and TCM enhanced viral replication in Ad.GS2-infected MSCs. SDF-1 is a stem cell homing factor. Our results suggest that the SDF-1/STAT3/TERT signaling axis in MSCs in response to the tumor microenvironment may contribute to the enhanced replication of Ad.GS2 carried by MSCs. Notably, we demonstrate the potent therapeutic efficacy of systemically delivered MSC-Ad.GS2 in pleural disseminated tumor and experimental metastasis models using intrapleural and tail vein injection of MBT-2 cells, respectively. Treatment with MSC-Ad.GS2 significantly reduced tumor growth and prolonged the survival of mice bearing metastatic bladder tumors. Since telomerase is expressed in a broad spectrum of cancers, this therapeutic strategy may be broadly applicable. C1 [Yang, Mei-Lin; Shiau, Ai-Li; Wu, Chao-Liang] Chia Yi Christian Hosp, Ditmanson Med Fdn, Dept Med Res, Chiayi, Taiwan. [Yang, Mei-Lin; Shiau, Ai-Li] Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, Tainan 70101, Taiwan. [Hu, Che-Yuan; Shieh, Gia-Shing] Natl Cheng Kung Univ, Coll Med, Dept Urol, Tainan, Taiwan. [Lee, Ya-Che; Chen, Pi-Che] Chia Yi Christian Hosp, Ditmanson Med Fdn, Dept Urol, Chiayi, Taiwan. [Chang, Chao-Ching; Chen, Yi-Cheng; Lee, Pei-Ru; Wu, Chao-Liang] Natl Cheng Kung Univ, Coll Med, Dept Biochem & Mol Biol, Tainan 70101, Taiwan. [Su, Bing-Hua] Taipei Med Univ, Coll Med, Sch Resp Therapy, Taipei, Taiwan. [Shieh, Gia-Shing] Tainan Hosp, Dept Urol, Dept Hlth, Tainan 70043, Taiwan. [Wu, Pensee] Keele Univ, Sch Med, Keele, Staffs, England. [Wu, Pensee] Univ Hosp North Midlands, Dept Obstet & Gynaecol, Newcastle Upon Lyme, Staffs, England. C3 National Cheng Kung University; National Cheng Kung University; National Cheng Kung University; Taipei Medical University; Keele University RP Shiau, AL (corresponding author), Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, Tainan 70101, Taiwan.; Wu, CL (corresponding author), Natl Cheng Kung Univ, Coll Med, Dept Biochem & Mol Biol, Tainan 70101, Taiwan.; Shieh, GS (corresponding author), Tainan Hosp, Dept Urol, Dept Hlth, Tainan 70043, Taiwan. EM alshiau@mail.ncku.edu.tw; 00053@tnhosp.mohw.gov.tw; wumolbio@mail.ncku.edu.tw RI Wu, Pensée/ABD-2931-2020; Hu, Che-Yuan/AGP-5540-2022; shiau, A-Li/C-2885-2012; Chang, Chien-Hsiang/HKM-5747-2023; Yang, Mei-Lin/KCJ-8685-2024 OI Yang, Mei-Lin/0000-0001-8102-2161; Hu, Che Yuan/0000-0001-5151-4552; FU Ditmanson Medical Foundation Chia-Yi Christian Hospital [NCKUCYC-P-11101]; National Science and Technology Council, Taiwan [108-2320-B-006-026, 112-2314-B-006-045] FX This work was in part supported by research grants from Ditmanson Medical Foundation Chia-Yi Christian Hospital (NCKUCYC-P-11101) and National Science and Technology Council, Taiwan (108-2320-B-006-026 and 112-2314-B-006-045). 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Oncolytic-reovirus is an attractive anti-cancer therapeutic agent for clinical testing. Many studies used mesenchymal stem cells (MSCs) as a carrier cell to enhance the delivery and quality of treatment with oncolytic-virotherapy. But, biosynthetic capacity and behavior of cells in response to viral infections are different. The infecting process of reoviruses takes from two-hours to one-week, depends on host cell and the duration of different stages of virus replication cycle. The latter includes the binding of virus particle, entry, uncoating, assembly and release of progeny-viruses. We evaluated the timing and infection cycle of reovirus type-3 strain Dearing (T3D), using one-step replication experiment by molecular and conventional methods in MSCs and L929 cell as control. Materials and Methods: In this experimental study, L929 and adipose-derived MSCs were infected with different multiplicities of infection (MOI) of reovirus T3D. At different time points, the quantity of progeny viruses has been measured using virus titration assay and quantitative real-time polymerase chain reaction (qRT-PCR) to investigate the ability of these cells to support the reovirus replication. One-step growth cycle were examined by 50% cell culture infectious dose (CCID50) and qRT-PCR. Results: The growth curve of reovirus in cells shows that MOI: 1 might be optimal for virus production compared to higher and lower MOIs. The maximum quantity of virus production using MOI: 1 was achieved at 48-hours post-infection. The infectious virus titer became stationary at 72-hours post-infection and then gradually decreased. The virus cytopathic effect was obvious in MSCs and this cells were susceptible to reovirus infection and support the virus replication. Conclusion: Our data highlights the timing schedule for reovirus replication, kinetics models and burst size. Further investigation is recommended to better understanding of the challenges and opportunities, for using MSCs loaded with reovirus in cancer-therapy. C1 [Banijamali, Razieh Sadat; Soleimanjahi, Hoorieh; Karimi, Hesam; Khorrami, Seyed Mahmood Seyed] Tarbiat Modares Univ, Fac Med Sci, Dept Virol, Tehran, Iran. [Soudi, Sara] Tarbiat Modares Univ, Fac Med Sci, Dept Immunol, Tehran, Iran. [Abdoli, Asghar] Pasteur Inst Iran, Dept Hepatitis & AIDS, Tehran, Iran. [Zandi, Keivan] Emory Univ, Ctr AIDS Res, Dept Pediat, Lab Biochem Pharmacol,Sch Med, Atlanta, GA USA. C3 Tarbiat Modares University; Tarbiat Modares University; Pasteur Network; Pasteur Institute of Iran; Emory University RP Soleimanjahi, H (corresponding author), Tarbiat Modares Univ, Fac Med Sci, Dept Virol, Tehran, Iran. EM soleim_h@modares.ac.ir RI Soleimanjahi, Hoorieh/Y-7846-2019; Soleimanjahi, Hoorieh/B-8945-2017; Lei, Yu/ABF-1293-2020 OI Soleimanjahi, Hoorieh/0000-0003-1931-7801; Seyed Khorami, Seyed Mahmood/0000-0002-5043-8292; FU Tarbiat Modares University; Tarbiat Modares University, Faculty of Medical Sciences [52/7400]; NIMAD (National Institute for Medical Research Development) [957970] FX We wish to thank deputy of research, Tarbiat Modares University for their financial support and providing assistance. The results described in this manuscript were part of student thesis, which was supported by the grant number 52/7400 from the Research Deputy of Tarbiat Modares University, Faculty of Medical Sciences, and partially supported by NIMAD (National Institute for Medical Research Development) the grant number of 957970. The authors declare that they have no competing interests. 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PD FAL PY 2020 VL 22 IS 3 BP 283 EP 292 DI 10.22074/cellj.2020.6686 PG 10 WC Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology GA KC7GN UT WOS:000507341800004 PM 31863653 DA 2025-10-02 ER PT J AU Zhang, YN Liu, C Wang, T Kong, FX Zhang, H Yi, J Dong, XW Duan, H Tao, N Yang, YF Wang, H AF Zhang, Yuning Liu, Chao Wang, Tao Kong, Fanxuan Zhang, Huan Yi, Jing Dong, Xiwen Duan, Han Tao, Ning Yang, Yuefeng Wang, Hua TI Therapeutic effects of mesenchymal stem cells loaded with oncolytic adenovirus carrying decorin on a breast cancer lung metastatic mouse model SO MOLECULAR THERAPY ONCOLYTICS LA English DT Article ID PREFERENTIAL SITE; GROWTH; BETA; SUBTYPES; TRIAL; RISK AB Oncolytic adenoviruses (OAds) are alternative immune therapeutic strategies for tumors. However, liver uptake and antibody neutralization are two major barriers for systemic delivery during the treatment of tumor metastasis. Mesenchymal stem cells (MSCs) have emerged as potential vehicles to improve delivery. In this study, we loaded umbilical-cord-derived MSCs (UC-MSCs) with OAds expressing decorin (rAd.DCN) or without foreign genes (rAd.Null) to treat breast cancer lung metastasis. In vivo, rAd.Null, MSCs.Null, and rAd.DCN exhibited antitumor effects compared with other groups in a mouse model. Unexpectedly, MSCs.Null showed much greater antitumor responses than MSCs.DCN, including improved survival and reduced tumor burden. Compared with rAd.Null, both MSCs.Null and MSCs.DCN could improve the viral spread and distribution in metastatic tumor lesions in the lung. MSCs.DCN produced much more decorin in lungs than rAd.DCN; however, rAd.DCN reduced the downstream target genes of decorin much more strongly than MSCs.DCN, which was consistent with in vitro findings. In addition, rAd.DCN, MSCs.Null, and MSCs.DCN could reduce The cytokine levels in the lung. In conclusion, MSCs improved oncolytic adenoviral delivery and spread in tumor tissues and enhanced therapeutic effects. However, MSCs.DCN reduced OAd-evoked antitumor responses, possibly via a contact-dependent mechanism. C1 [Zhang, Yuning; Liu, Chao; Kong, Fanxuan; Yi, Jing; Dong, Xiwen; Duan, Han; Tao, Ning; Wang, Hua] Beijing Inst Radiat Med, Dept Expt Haematol, 27 Taiping Rd, Beijing 100850, Peoples R China. [Wang, Tao] Peoples Liberat Army Gen Hosp, Oncol Dept, Med Ctr 5, Beijing 100071, Peoples R China. [Kong, Fanxuan] PLA Strateg Support Force Characterist Med Ctr, Beijing 100101, Peoples R China. [Zhang, Huan] Capital Med Univ, Beijing Tongren Hosp, Dept Crit Care Med, Beijing 100730, Peoples R China. [Yang, Yuefeng] Univ Chinese Acad Sci, HwaMei Hosp, Dept Expt Med Sci, Ningbo 315000, Zhejiang, Peoples R China. C3 Academy of Military Medical Sciences - China; Chinese People's Liberation Army General Hospital; Capital Medical University; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS RP Wang, H (corresponding author), Beijing Inst Radiat Med, Dept Expt Haematol, 27 Taiping Rd, Beijing 100850, Peoples R China.; Yang, YF (corresponding author), Univ Chinese Acad Sci, HwaMei Hosp, Dept Expt Med Sci, Ningbo 315000, Zhejiang, Peoples R China. EM yuefengyang1981@163.com; 18511712135@163.com RI ; Kong, Fanxuan/AAE-6847-2019; Dong, Xiwen/KVB-1648-2024; Wang, Tao/AAT-3028-2020; Tao, Ning/AAK-7068-2021 OI Zhang, Yuning/0000-0002-6368-7685; tao, ning/0000-0003-4811-3090; zhang, huan/0000-0002-5332-3335 FU Natural Science Foundation of Zhe-jiang Province [LY19H160010]; Opened-end Fund of Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province [2019E10020, KFJJ-202003] FX ACKNOWLEDGMENTS This work was supported by the Natural Science Foundation of Zhe-jiang Province (no. LY19H160010) and the Opened-end Fund of Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, 2019E10020 (KFJJ-202003) . 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Ther. Oncolytics PD MAR 17 PY 2022 VL 24 BP 486 EP 496 DI 10.1016/j.omto.2022.01.007 EA FEB 2022 PG 11 WC Oncology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Research & Experimental Medicine GA ZZ5XB UT WOS:000773340200002 PM 35229027 OA gold, Green Published DA 2025-10-02 ER PT J AU Delgado-Bonet, P Tomeo-Martín, BD Ortiz-Díez, G Perisé-Barrios, AJ AF Delgado-Bonet, Pablo Davinia Tomeo-Martin, Beatriz Ortiz-Diez, Gustavo Judith Perise-Barrios, Ana TI Tumor-Homing of Mesenchymal Stem Cells Infected with Oncolytic Virus in a Canine Patient SO VETERINARY SCIENCES LA English DT Article DE Celyvir; oncolytic virus; tumor-homing; virotherapy ID ADENOVIRUS; VIROTHERAPY; THERAPY; DELIVERY; ICOVIR-5; TRIAL AB Intravenous administration of oncolytic adenovirus (OAds) can be challenging, although various vehicles for the delivery of the virus to the tumor have been described. The efficacy of mesenchymal stem cells (MSCs) as a virus vehicle has been reported in mouse models and canine and human patients, but the actual action mechanism has never been described in patients. It is of importance to determine whether MSCs infected with OAds can reach the tumor and release the virus in a clinical setting. For this purpose, GFP-labeled MSCs were infected with an OAd and inoculated into a companion dog diagnosed with spontaneous lung carcinoma. Forty-eight hours later, the tumor was excised and analyzed microscopically by flow cytometry for GFP fluorescence detection, and a cellular culture was established. Peripheral blood samples were taken to quantify the oncolytic adenovirus by qRT-PCR. Green fluorescence cells detected in the cellular culture by microscopy and flow cytometry revealed 0.69% GFP-positive cells in the tumor. OAd in peripheral blood was confirmed by qRT-PCR during follow-up. For the first time, the tumoral-homing capacity of OAds infected-MSC has been confirmed in a clinical setting, helping to explain the clinical response mechanism, whose efficacy was previously reported in canine and human patients. C1 [Delgado-Bonet, Pablo; Davinia Tomeo-Martin, Beatriz; Judith Perise-Barrios, Ana] Univ Alfonso X Sabio, Biomed Res Unit, Villanueva De La Canada 28691, Spain. [Ortiz-Diez, Gustavo] Univ Complutense Madrid, Vet Teaching Hosp, Small Anim Surg Serv, Madrid 28040, Spain. C3 Universidad Alfonso X el Sabio (UAX); Complutense University of Madrid RP Perisé-Barrios, AJ (corresponding author), Univ Alfonso X Sabio, Biomed Res Unit, Villanueva De La Canada 28691, Spain. EM pdelgbon@uax.es; btomemar@uax.es; gusortiz@ucm.es; aperibar@uax.es RI ; Perisé Barrios, Ana Judith/A-4007-2019 OI Perise Barrios, Ana Judith/0000-0002-0136-3968; Delgado-Bonet, Pablo/0000-0002-6638-3863; Tomeo-Martin, Beatriz Davinia/0000-0002-7720-4162; Ortiz-Diez, Gustavo/0000-0002-8242-2658 FU Universidad Alfonso X el Sabio; Santander UniversidadesFundacion Universidad Alfonso X el Sabio [1.010.909, PEJD-2019 PRE_BMD-16840]; Comunidad de Madrid FX This research was funded by Universidad Alfonso X el Sabio and by Santander UniversidadesFundacion Universidad Alfonso X el Sabio (1.010.909 grant to A.J.P-B.), whose support we gratefully acknowledge. B.D.T-M has a predoctoral fellow (PEJD-2019 PRE_BMD-16840) funded by Comunidad de Madrid. 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Their potential in cancer therapy highlights the need for a consistent and renewable source for the production of uniform human MSCs suitable for clinical applications. In this study, we seek to investigate whether human embryonic stem cells can be used as a cell source to fulfill this goal. We generated MSC-like cells from two human embryonic stem cell lines, HuES9 and H1, and observed that MSC-like cells derived from human embryonic stem cells were able to migrate into human glioma intracranial xenografts after being injected into the cerebral hemisphere contralateral to the tumor inoculation site. We engineered these cells with baculoviral and lentiviral vectors, respectively, for transient and stable expression of the herpes simplex virus thymidine kinase gene. In tumor-bearing mice the engineered MSC-like cells were capable of inhibiting tumor growth and prolonging survival in the presence of ganciclovir after they were injected either directly into the xenografts or into the opposite hemisphere. Our findings suggest that human embryonic stem cell-derived MSCs may be a viable and attractive alternative for large-scale derivation of targeting vehicles for cancer therapy. C1 [Bak, Xiao Ying; Lam, Dang Hoang; Yang, Jingye; Ye, Kai; Wei, Esther Lee Xing; Wang, Shu] Inst Bioengn & Nanotechnol, Singapore 117602, Singapore. [Yang, Jingye; Wang, Shu] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore. [Lim, Sai Kiang] Inst Med Biol, Singapore 138648, Singapore. C3 Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Bioengineering & Bioimaging (IBB); A*STAR - Institute of Bioengineering & Nanotechnology (IBN); National University of Singapore; Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Medical Biology (IMB) RP Wang, S (corresponding author), Inst Bioengn & Nanotechnol, 31 Biopolis Way,Nanos 04-01, Singapore 138669, Singapore. EM dbsws@nus.edu.sg RI wang, shu/H-6744-2012; Lim, Sai Kiang/AEN-0252-2022 OI Lim, Sai Kiang/0000-0002-5752-3297 FU Institute of Bioengineering and Nanotechnology; Biomedical Research Council; Agency for Science, Technology, and Research (A*STAR) in Singapore; Ministry of Education of Singapore [T206B3110]; National Medical Research Council in Singapore [NMRC/1203/2009] FX This work was supported by the Institute of Bioengineering and Nanotechnology, the Biomedical Research Council, and the Agency for Science, Technology, and Research (A*STAR) in Singapore and by grants from the Ministry of Education of Singapore (T206B3110) and the National Medical Research Council in Singapore (NMRC/1203/2009). 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Gene Ther. PD NOV PY 2011 VL 22 IS 11 BP 1365 EP 1377 DI 10.1089/hum.2010.212 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 852QS UT WOS:000297373100008 PM 21425958 OA Green Submitted DA 2025-10-02 ER PT J AU Jazowiecka-Rakus, J Sochanik, A Rusin, A Hadrys, A Fidyk, W Villa, N Rahman, MM Chmielik, E Franco, LS McFadden, G AF Jazowiecka-Rakus, Joanna Sochanik, Aleksander Rusin, Aleksandra Hadrys, Agata Fidyk, Wojciech Villa, Nancy Rahman, Masmudur M. Chmielik, Ewa Franco, Lina S. McFadden, Grant TI Myxoma Virus-Loaded Mesenchymal Stem Cells in Experimental Oncolytic Therapy of Murine Pulmonary Melanoma SO MOLECULAR THERAPY-ONCOLYTICS LA English DT Article ID TUMOR-INITIATING CELLS; CANCER-CELLS; VIROTHERAPY; DELIVERY; APOPTOSIS; SURVIVAL; GROWTH AB Oncolytic viruses can target neoplasms, triggering oncolytic and immune effects. Their delivery to melanoma lesions remains challenging. Bone-marrow-derived mesenchymal stem cells (MSCs) were shown to be permissive for oncolytic myxoma virus (MYXV), allowing its transfer to melanoma cells, leading to their killing. Involvement of progeny virus was demonstrated in the transfer from MSCs to co-cultured melanoma cells. The inhibitory effect of virus on melanoma foci formation in murine lungs was revealed using melanoma cells previously co-cultured with MYXV-infected MSCs. Virus accumulation and persistence in lungs of lesion-bearing mice were shown following intravenous administration of MSC-shielded MYXV construct encoding luciferase. Therapy of experimentally induced lung melanoma in mice with interleukin (IL)-15-carrying MYXV construct delivered by MSCs led to marked regression of lesions and could increase survival. Elevated natural killer (NK) cell percentages in blood indicated robust innate responses against unshielded virus only. Lung infiltration by NK cells was followed by inflow of CD8+ T lymphocytes into melanoma lesions. Elevated expression of genes involved in adaptive immune response following oncolytic treatment was confirmed using RT-qPCR. No adverse pathological effects related to MSC-mediated oncolytic therapy with MYXV were observed. MSCs allow for safe and efficient ferrying of therapeutic MYXV to pulmonary melanoma foci triggering immune effects. C1 [Jazowiecka-Rakus, Joanna; Sochanik, Aleksander; Rusin, Aleksandra; Hadrys, Agata; Fidyk, Wojciech; Chmielik, Ewa] Maria Sklodowska Curie Mem Natl Res Inst Oncol, PL-44102 Gliwice, Poland. [Villa, Nancy; Rahman, Masmudur M.; Franco, Lina S.; McFadden, Grant] Arizona State Univ, Biodesign Inst, Tempe, AZ 85287 USA. C3 Arizona State University; Arizona State University-Tempe RP Jazowiecka-Rakus, J (corresponding author), Maria Sklodowska Curie Mem Natl Res Inst Oncol, PL-44102 Gliwice, Poland. EM joanna.jazowiecka@io.gliwice.pl RI ; Rusin, Aleksandra/AAL-1422-2020; Fidyk, Wojciech/X-1469-2018 OI Sochanik, Aleksander/0000-0003-2674-246X; Fidyk, Wojciech/0000-0002-5953-7131; Kawulok, Agata/0000-0002-3315-428X; Chmielik, Ewa/0000-0001-8316-0541; Rusin, Aleksandra/0000-0003-0881-5995; Jazowiecka-Rakus, Joanna/0000-0001-5558-6115 FU National Science Centre, Krakow, Poland [2016/22/M/NZ6/00418]; International Centre for Genetic Engineering and Biotechnology, Trieste, Italy [CRP/POL16-02_EC] FX The authors thank Krzysztof Rakus for technical guidance and discussion and Mario Abrantes, Marlena Pa~zdzior, Roman Lamch, and Lucyna Ponge for technical assistance. This study was supported by a grant from the National Science Centre, Krakow, Poland (no. 2016/22/M/NZ6/00418) and by a grant from the International Centre for Genetic Engineering and Biotechnology, Trieste, Italy (no. CRP/POL16-02_EC). 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Ther.-Oncolytics PD SEP 25 PY 2020 VL 18 BP 335 EP 350 DI 10.1016/j.omto.2020.07.003 PG 16 WC Oncology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Research & Experimental Medicine GA NW7AL UT WOS:000575168700028 PM 32775618 OA Green Submitted, gold DA 2025-10-02 ER PT J AU Choi, S Hong, JA Choi, HJ Song, JJ AF Choi, Soojin Hong, Jeong A. Choi, Hye Jin Song, Jae J. TI Enhanced tumor targeting and timely viral release of mesenchymal stem cells/oncolytic virus complex due to GRP78 and inducible E1B55K expressions greatly increase the antitumor effect of systemic treatment SO MOLECULAR THERAPY ONCOLYTICS LA English DT Article ID GROWTH-FACTOR-BETA; REGULATED PROTEIN 78; TGF-BETA; ONCOLYTIC ADENOVIRUS; STROMAL CELLS; REPLICATION; MIGRATION; HSP27; MICROENVIRONMENT; DEGRADATION AB Systemic delivery of oncolytic viruses has been widely regarded as an impractical option for antitumor treatment. Here, we selected two target genes as leading components, and significant therapeutic effects were obtained by simultaneously reducing the expression of transforming growth factor beta 1 (TGF-beta 1) and heat shock protein 27 (HSP27) in various cancer cell types. Downregulation of HSP27 reduced the cellular levels of tumor progression-related proteins, and the simultaneous downregulation of HSP27 and TGF-beta 1 increased tumor cell death beyond that observed with TGF-beta 1 downregulation alone. To increase the potential for systemic administration, we generated modified mesenchymal stem cells (MSCs) to act as oncolytic adenovirus factories and carriers and assessed bioavailability in tumors after MSC injection. The MSCs were modified to express 78-kDa glucose-regulated protein (GRP78) and adenovirus early-region 1B 55 kDa (E1B55K). The tightly controlled inducible system permitted selective timing of viral release from carrier MSCs within the tumor. This approach significantly improved viral production, tumor targeting, timely viral release at the tumor site, and antitumor efficacy of the oncolytic adenovirus. These combined results demonstrate that engineered MSCs can significantly enhance the antitumor effects of oncolytic viruses without adverse safety issues, which may greatly extend the clinical applicability of oncolytic adenoviruses. C1 [Choi, Soojin; Hong, Jeong A.; Song, Jae J.] Yonsei Univ Coll Med, Severance Biomed Sci Inst, Seoul 03722, South Korea. [Choi, Soojin; Hong, Jeong A.; Song, Jae J.] Yonsei Univ Coll Med, Inst Canc Res, Seoul 03722, South Korea. [Choi, Hye Jin] Yonsei Univ Coll Med, Dept Internal Med, Seoul 03722, South Korea. [Song, Jae J.] Yonsei Univ, Grad Sch Med Sci, Seoul 03722, South Korea. [Choi, Soojin; Hong, Jeong A.] Yonsei Univ Coll Med, Grad Sch Med Sci, Brain Korea 21 Project, Seoul 03722, South Korea. [Song, Jae J.] Dates Bio Co Ltd, Seoul, South Korea. C3 Yonsei University; Yonsei University Health System; Yonsei University; Yonsei University Health System; Yonsei University; Yonsei University Health System; Yonsei University; Yonsei University; Yonsei University Health System RP Choi, HJ (corresponding author), Yonsei Univ, Dept Internal Med, 50-1 Yonsei Ro, Seoul 03722, South Korea.; Song, JJ (corresponding author), Yonsei Univ, Severance Biomed Sci Inst, 50-1 Yonsei Ro, Seoul 03722, South Korea. EM choihj@yuhs.ac; jjs109@yuhs.ac RI Song, Myungjae/A-1392-2017 OI Song, Jae/0000-0001-8183-9550; Choi, Soojin/0009-0007-7996-0192; CHOI, HYE JIN/0000-0001-5917-1400 FU Bio and Medical Technology Development Program of the National Research Foundation (NRF); Korean government (Ministry of Science and ICT [MSIT]) [NRF-2019M3E5D5064554]; National Research Foundation of Korea (NRF) - Korea government (MSIT) [NRF-2020R1A2C1005245]; Korea Drug Development Fund - MSIT; Ministry of Trade, Industry, and Energy; Ministry of Health and Welfare (Republic of Korea) [HN21C0960]; Yonsei University College of Medicine [6-2021-0079] FX We thank Medical Illustration and Design, part of the Medical Research Support Services of Yonsei University College of Medicine, for all artistic support related to this work. This research was supported by the Bio and Medical Technology Development Program of the National Research Foundation (NRF) and funded by the Korean government (Ministry of Science and ICT [MSIT]) (NRF-2019M3E5D5064554). This work was also supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2020R1A2C1005245). This research was also supported by the Korea Drug Development Fund funded by MSIT; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare (HN21C0960, Republic of Korea). Finally, this study was also supported by a faculty research grant from Yonsei University College of Medicine (6-2021-0079). 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Ther. Oncolytics PD DEC 15 PY 2022 VL 27 BP 26 EP 47 DI 10.1016/j.omto.2022.09.004 EA OCT 2022 PG 22 WC Oncology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Research & Experimental Medicine GA 8J3HC UT WOS:000922309900002 PM 36247810 OA Green Published, gold DA 2025-10-02 ER PT J AU Yong, RL Shinojima, N Fueyo, J Gumin, J Vecil, GG Marini, FC Bogler, O Andreeff, M Lang, FF AF Yong, Raymund L. Shinojima, Naoki Fueyo, Juan Gumin, Joy Vecil, Giacomo G. Marini, Frank C. Bogler, Oliver Andreeff, Michael Lang, Frederick F. TI Human Bone Marrow-Derived Mesenchymal Stem Cells for Intravascular Delivery of Oncolytic Adenovirus Δ24-RGD to Human Gliomas SO CANCER RESEARCH LA English DT Article ID TARGETED-DELIVERY; PROGENITOR CELLS; TUMOR; VEHICLES; TROPISM; VECTOR; CANCER; TEMOZOLOMIDE; MECHANISMS; ADHESION AB Delta 24-RGD is an infectivity-augmented, conditionally replicative oncolytic adenovirus with significant antiglioma effects. Although intratumoral delivery of Delta 24-RGD may be effective, intravascular delivery would improve successful application in humans. Due to their tumor tropic properties, we hypothesized that human mesenchymal stem cells (hMSC) could be harnessed as intravascular delivery vehicles of Delta 24-RGD to human gliomas. To assess cellular events, green fluorescent protein-labeled hMSCs carrying Delta 24-RGD (hMSC-Delta 24) were injected into the carotid artery of mice harboring orthotopic U87MG or U251-V121 xenografts and brain sections were analyzed by immunofluorescence for green fluorescent protein and viral proteins (EIA and hexon) at increasing times. hMSC-Delta 24 selectively localized to glioma xenografts and released Delta 24-RGD, which subsequently infected glioma cells. To determine efficacy, mice were implanted with luciferase-labeled glioma xenografts, treated with hMSC-Delta 24 or controls, and imaged weekly by bioluminescence imaging. Analysis of tumor size by bioluminescence imaging showed inhibition of glioma growth and eradication of tumors in hMSC-Delta 24-treated animals compared with controls (P < 0.0001). There was an increase in median survival from 42 days in controls to 75.5 days in hMSC-Delta 24-treated animals (P < 0.0001) and an increase in survival beyond 80 days from 0% to 37.5%, respectively. We conclude that intra-arterially delivered hMSC-Delta 24 selectively localize to human gliomas and are capable of delivering and releasing Delta 24-RGD into the tumor, resulting in improved survival and tumor eradication in subsets of mice. [Cancer Res 2009;69(23):8932-40] C1 [Yong, Raymund L.; Shinojima, Naoki; Gumin, Joy; Vecil, Giacomo G.; Bogler, Oliver; Lang, Frederick F.] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. [Fueyo, Juan] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Marini, Frank C.; Andreeff, Michael] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Houston, TX 77030 USA. [Yong, Raymund L.; Shinojima, Naoki; Fueyo, Juan; Gumin, Joy; Vecil, Giacomo G.; Bogler, Oliver; Lang, Frederick F.] Univ Texas MD Anderson Canc Ctr, Brain Tumor Ctr, Houston, TX 77030 USA. [Yong, Raymund L.] Univ British Columbia, Dept Surg, Div Neurosurg, Vancouver, BC V6T 1W5, Canada. C3 University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of British Columbia RP Lang, FF (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Box 442,1515 Holcombe Blvd, Houston, TX 77030 USA. EM flang@mdanderson.org RI ; Bogler, Oliver/IAP-5833-2023; Marini, Frank/L-8018-2016; Shinojima, Naoki/AAW-3038-2021 OI Shinojima, Naoki/0000-0003-3352-7936; Fueyo, Juan/0000-0001-6941-2335; Bogler, Oliver/0000-0002-3700-0480; FU NCI NIH HHS [P01 CA055164, P50 CA 127001, CA-55164, CA-16672, CA-49639, P50 CA116199, R01 CA109451, P30 CA016672, CA-1094551, R01 CA115729, P50 CA127001, CA-116199, P01 CA049639] Funding Source: Medline CR Alemany R, 2000, J GEN VIROL, V81, P2605, DOI 10.1099/0022-1317-81-11-2605 Alonso MM, 2007, CANCER RES, V67, P11499, DOI 10.1158/0008-5472.CAN-07-5312 Bauerschmitz GJ, 2004, INT J CANCER, V111, P303, DOI 10.1002/ijc.20217 Chiocca EA, 2004, MOL THER, V10, P958, DOI 10.1016/j.ymthe.2004.07.021 Colter DC, 2000, P NATL ACAD SCI USA, V97, P3213, DOI 10.1073/pnas.070034097 Conget PA, 2000, EXP HEMATOL, V28, P382, DOI 10.1016/S0301-472X(00)00134-X DiGirolamo CM, 1999, BRIT J HAEMATOL, V107, P275, DOI 10.1046/j.1365-2141.1999.01715.x Dmitriev I, 1998, J VIROL, V72, P9706, DOI 10.1128/JVI.72.12.9706-9713.1998 Fidler IJ, 1999, CANCER METAST REV, V18, P387, DOI 10.1023/A:1006329410433 Fueyo J, 2000, ONCOGENE, V19, P2, DOI 10.1038/sj.onc.1203251 Fueyo J, 2003, J NATL CANCER I, V95, P652, DOI 10.1093/jnci/95.9.652 Hakkarainen T, 2007, HUM GENE THER, V18, P627, DOI 10.1089/hum.2007.034 Hall B, 2007, INT J HEMATOL, V86, P8, DOI 10.1532/IJH97.06230 Kirn D, 2001, GENE THER, V8, P89, DOI 10.1038/sj.gt.3301377 Klopp AH, 2007, CANCER RES, V67, P11687, DOI 10.1158/0008-5472.CAN-07-1406 Komarova S, 2006, MOL CANCER THER, V5, P755, DOI 10.1158/1535-7163.MCT-05-0334 Krasnykh V, 1998, J VIROL, V72, P1844, DOI 10.1128/JVI.72.3.1844-1852.1998 Lal S, 2000, J NEUROSURG, V92, P326, DOI 10.3171/jns.2000.92.2.0326 Lang FF, 2003, J CLIN ONCOL, V21, P2508, DOI 10.1200/JCO.2003.21.13.2508 Lieber A, 1997, J VIROL, V71, P8798, DOI 10.1128/JVI.71.11.8798-8807.1997 Nakamizo A, 2005, CANCER RES, V65, P3307, DOI 10.1158/0008-5472.CAN-04-1874 Nakamura K, 2004, GENE THER, V11, P1155, DOI 10.1038/sj.gt.3302276 Olmsted-Davis EA, 2002, HUM GENE THER, V13, P1337, DOI 10.1089/104303402760128568 Rubin JB, 2003, P NATL ACAD SCI USA, V100, P13513, DOI 10.1073/pnas.2235846100 Rüster B, 2006, BLOOD, V108, P3938, DOI 10.1182/blood-2006-05-025098 Segers VFM, 2006, AM J PHYSIOL-HEART C, V290, pH1370, DOI 10.1152/ajpheart.00523.2005 Sonabend AM, 2008, STEM CELLS, V26, P831, DOI 10.1634/stemcells.2007-0758 Steingen C, 2008, J MOL CELL CARDIOL, V44, P1072, DOI 10.1016/j.yjmcc.2008.03.010 Stoff-Khalili MA, 2007, BREAST CANCER RES TR, V105, P157, DOI 10.1007/s10549-006-9449-8 Studeny M, 2004, JNCI-J NATL CANCER I, V96, P1593, DOI 10.1093/jnci/djh299 Studeny M, 2002, CANCER RES, V62, P3603 Stupp R, 2005, NEW ENGL J MED, V352, P987, DOI 10.1056/NEJMoa043330 Szentirmai O, 2006, NEUROSURGERY, V58, P365, DOI 10.1227/01.NEU.0000195114.24819.4F Vilalta M, 2008, STEM CELLS DEV, V17, P993, DOI 10.1089/scd.2007.0201 NR 34 TC 198 Z9 235 U1 0 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2009 VL 69 IS 23 BP 8932 EP 8940 DI 10.1158/0008-5472.CAN-08-3873 PG 9 WC Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology GA 527JH UT WOS:000272362800014 PM 19920199 OA Green Submitted, Green Accepted, Bronze DA 2025-10-02 ER PT J AU Morales-Molina, A Rodríguez-Milla, MA Gimenez-Sanchez, A Perisé-Barrios, AJ García-Castro, J AF Morales-Molina, Alvaro Rodriguez-Milla, Miguel Angel Gimenez-Sanchez, Alicia Perise-Barrios, Ana Judith Garcia-Castro, Javier TI Cellular Virotherapy Increases Tumor-Infiltrating Lymphocytes (TIL) and Decreases their PD-1+Subsets in Mouse Immunocompetent Models SO CANCERS LA English DT Article DE oncolytic virus; adenovirus; MSCs; immunotherapy; Celyvir; TILs; T cells; PD-1; renal cancer; melanoma ID MESENCHYMAL STEM-CELLS; ONCOLYTIC ADENOVIRUS; EXPRESSION; PRB; NEUROBLASTOMA; ANGIOGENESIS; MODULATION; ICOVIR-5; EFFICACY; DELIVERY AB Oncolytic virotherapy uses viruses designed to selectively replicate in cancer cells. An alternative to intratumoral administration is to use mesenchymal stem cells (MSCs) to transport the oncolytic viruses to the tumor site. Following this strategy, our group has already applied this treatment to children and adults in a human clinical trial and a veterinary trial, with good clinical responses and excellent safety profiles. However, the development of immunocompetent cancer mouse models is still necessary for the study and improvement of oncolytic viroimmunotherapies. Here we have studied the antitumor efficacy, immune response, and mechanism of action of a complete murine version of our cellular virotherapy in mouse models of renal adenocarcinoma and melanoma. We used mouse MSCs infected with the mouse oncolytic adenovirus dlE102 (OAd-MSCs). In both models, treatment with OAd-MSCs significantly reduced tumor volumes by 50% and induced a pro-inflammatory tumor microenvironment. Furthermore, treated mice harboring renal adenocarcinoma and melanoma tumors presented increased infiltration of tumor-associated macrophages (TAMs), natural killer cells, and tumor-infiltrating lymphocytes (TILs). Treated mice also presented lower percentage of TILs expressing programmed cell death protein 1 (PD-1)-the major regulator of T cell exhaustion. In conclusion, treatment with OAd-MSCs significantly reduced tumor volume and induced changes in tumor-infiltrating populations of melanoma and renal cancer. C1 [Morales-Molina, Alvaro; Rodriguez-Milla, Miguel Angel; Gimenez-Sanchez, Alicia; Perise-Barrios, Ana Judith; Garcia-Castro, Javier] Inst Salud Carlos III, Cellular Biotechnol Unit, E-28220 Madrid, Spain. [Perise-Barrios, Ana Judith] Univ Alfonso X Sabio, Biomed Res Unit, E-28691 Madrid, Spain. C3 Instituto de Salud Carlos III; Universidad Alfonso X el Sabio (UAX) RP García-Castro, J (corresponding author), Inst Salud Carlos III, Cellular Biotechnol Unit, E-28220 Madrid, Spain. EM alvaromorales102@gmail.com; rmilla@isciii.es; aliciags89@gmail.com; aperibar@uax.es; jgcastro@isciii.es RI Garcia-Castro, Javier/ABC-9741-2021; Perisé Barrios, Ana Judith/A-4007-2019; Garcia-Castro, Javier/H-5274-2011 OI Garcia-Castro, Javier/0000-0001-7604-1640; Perise Barrios, Ana Judith/0000-0002-0136-3968; Morales-Molina, Alvaro/0000-0003-4532-7667 FU Ministerio de Economia y Competitividad of Spain [PI14CIII/00005, PI17CIII/00013]; Consejeria de Educacion, Juventud y Deporte of Comunidad de Madrid [P2017/BMD-3692]; Fundacion Oncohematologia Infantil; Asociacion Pablo Ugarte; AFANION FX This study was funded by the Ministerio de Economia y Competitividad of Spain (grant numbers PI14CIII/00005 and PI17CIII/00013), Consejeria de Educacion, Juventud y Deporte of Comunidad de Madrid (grant number P2017/BMD-3692), Fundacion Oncohematologia Infantil, AFANION, and Asociacion Pablo Ugarte, whose support we gratefully acknowledge. 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It was shown that monotherapy alone is largely ineffective. The combination therapy was used for antitumor activity. The synergistic anticancer effects of oncolytic reovirus-infected secretome in combination with irinotecan and metformin are evaluated in vitro. The aim of research was to assess anticancer impacts of ReoT3D, irinotecan, metformin in combination, against murine colorectal cancer cells (CT26). Methods: The L929 and the CT26 colorectal cancerous cell lines were treated in vitro with irinotecan, metformin, the Dearing strain of reovirus serotype 3 (ReoT3D) (V), and the secretome of intact (S) or reovirus-infected murine adipose-derived mesenchymal stem cells (SV). The cell viability was measured by MTT, and the apoptosis rate was analyzed by annexin V-FITC staining and flow cytometry 48 and 72 h after treatment. Results: We found that cells exposed to a combination of SV+Met+I had significantly lower cell viability and higher apoptosis rates as compared to cells exposed to Met+I, 48 and 72 h. These results suggest that metformin in combination with irinotecan and reovirus produces a synergistic effect on cell death, and adding reovirus-infected secretome (SV) to a Met+I regimen induces a higher apoptosis rate compared to Met+I alone. Based on the results, the combination of SV+Met+I has induced more apoptosis than S, SV, SV+I, and SV+Met. Also, all of the combined treatments induced apoptosis significantly versus secretome alone. Discussion: In this in vitro study, we found that the combination of T3D reovirus (oncolytic virus) and metformin with the anticancer drug irinotecan resulted in higher rates of growth inhibition and apoptosis induction in the colorectal cancer cell line. This synergistic effect was even more pronounced when using the combination of secretome derived from reovirus-infected AD-MSCs, metformin, and irinotecan. Conclusion: We highlight that the combination of ReoT3D-derived secretome with irinotecan and metformin showed a synergistic anticancer effect on the CT26 cell line, and this strategy may be considered as a new approach against colorectal cancer in the in vitro and in vivo in future studies. (c) 2024 The Author(s).Published by S. Karger AG, Basel C1 [Elhamipour, Maliheh; Soleimanjahi, Hoorieh; Sharifi, Negar; Karimi, Hesam] Tarbiat Modares Univ, Fac Med Sci, Dept Virol, Tehran, Iran. [Abdoli, Asghar; Karimi, Hesam] Pasteur Inst Iran, Dept Hepatitis & AIDS, Tehran, Iran. [Jahi, Saeed Soleyman] Washington Univ St Louis, Div Gastroenterol, Sch Med, St Louis, MO USA. [Kvistad, Ruth] Univ Missouri St Louis, Dept Biol, St Louis, MO USA. [Kvistad, Ruth] Univ Missouri St Louis, Dept Chem & Biochem, St Louis, MO USA. C3 Tarbiat Modares University; Pasteur Network; Pasteur Institute of Iran; Washington University (WUSTL); University of Missouri System; University of Missouri Saint Louis; University of Missouri System; University of Missouri Saint Louis RP Soleimanjahi, H (corresponding author), Tarbiat Modares Univ, Fac Med Sci, Dept Virol, Tehran, Iran. EM soleim_h@modares.ac.ir RI Soleimanjahi, Hoorieh/Y-7846-2019; Soleimanjahi, Hoorieh/B-8945-2017; Abdoli, Asghar/I-6280-2018 OI Soleimanjahi, Hoorieh/0000-0003-1931-7801; FU Research Deputy of Tarbiat Modares University, Faculty of Medical Sciences [Med-75118] FX The results described in this paper were part of student thesis,which was supported by the Grant No. Med-75118 from the Research Deputy of Tarbiat Modares University, Faculty of Medical Sciences. 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Rolle, Cleo E. Tyler, Matthew A. Han, Yu Sengupta, Sadhak Wainwright, Derek A. Balyasnikova, Irina V. Ulasov, Ilya V. Lesniak, Maciej S. TI Bone Marrow Mesenchymal Stem Cells Loaded With an Oncolytic Adenovirus Suppress the Anti-adenoviral Immune Response in the Cotton Rat Model SO MOLECULAR THERAPY LA English DT Article ID STROMAL CELLS; SURVIVIN PROMOTER; IN-VITRO; PROLIFERATION; INHIBIT; IDENTIFICATION; EXPANSION; BRAIN AB Oncolytic adenoviral virotherapy is an attractive treatment modality for cancer. However, following intratumoral injections, oncolytic viruses fail to efficiently migrate away from the injection site and are rapidly cleared by the immune system. We have previously demonstrated enhanced viral delivery and replicative persistence in vivo using human bone marrow-derived mesenchymal stem cells (MSCs) as delivery vehicles. In this study, we evaluated the immune response to adenovirus (Ad)-loaded MSCs using the semipermissive cotton rat (CR) model. First, we isolated MSCs from CR bone marrow aspirates. Real-time quantitative PCR analysis revealed that CR MSCs supported the replication of Ads in vitro. Moreover, we observed similar levels of suppression of T-cell proliferation in response to mitogenic stimulation, by MSCs alone and virus-loaded MSCs. Additionally, we found that MSCs suppressed the production of interferon-gamma (IFN-gamma) by activated T cells. In our in vivo model, CR MSCs enhanced the dissemination and persistence of Ad, compared to virus injection alone. Collectively, our data suggest that the use of MSCs as a delivery strategy for oncolytic Ad potentially offers a myriad of benefits, including improved delivery, enhanced dissemination, and increased persistence of viruses via suppression of the antiviral immune response. C1 [Ahmed, Atique U.; Rolle, Cleo E.; Tyler, Matthew A.; Han, Yu; Sengupta, Sadhak; Wainwright, Derek A.; Balyasnikova, Irina V.; Ulasov, Ilya V.; Lesniak, Maciej S.] Univ Chicago, Brain Tumor Ctr, Chicago, IL 60637 USA. C3 University of Chicago RP Lesniak, MS (corresponding author), Univ Chicago, Brain Tumor Ctr, 5841 S Maryland Ave,MC 3026, Chicago, IL 60637 USA. EM mlesniak@surgery.bsd.uchicago.edu RI Ulasov, Ilya/A-2352-2014; Sengupta, Sadhak/D-2526-2009; Yu, Jinghua/L-3794-2017; Ahmed, Atique/HNS-0597-2023 OI Ulasov, Ilya/0000-0002-0818-0363; Wainwright, Derek/0000-0001-7232-4264; Ahmed, Atique/0000-0003-4795-0188; FU National Cancer Institute [R01-CA122930]; National Institute of Neurological Disorders and Stroke [K08-NS046430]; Alliance for Cancer Gene Therapy Young Investigator Award; American Cancer Society [RSG-07-276-01-MGO] FX This work was supported by the National Cancer Institute (R01-CA122930), the National Institute of Neurological Disorders and Stroke (K08-NS046430), The Alliance for Cancer Gene Therapy Young Investigator Award, and the American Cancer Society (RSG-07-276-01-MGO). 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Ther. PD OCT PY 2010 VL 18 IS 10 BP 1846 EP 1856 DI 10.1038/mt.2010.131 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 659BE UT WOS:000282541200016 PM 20588259 OA Green Published, Green Accepted, hybrid DA 2025-10-02 ER PT J AU Nilson, R Lübbers, O Schmidt, CQ Rojewski, M Zeplin, PH Funk, W Schrezenmeier, H Kritzinger, A Kochanek, S Krutzke, L AF Nilson, Robin Luebbers, Olivia Schmidt, Christoph Q. Rojewski, Markus Zeplin, Philip Helge Funk, Wolfgang Schrezenmeier, Hubert Kritzinger, Astrid Kochanek, Stefan Krutzke, Lea TI Hexon modification of human adenovirus type 5 vectors enables efficient transduction of human multipotent mesenchymal stromal cells SO MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT LA English DT Article ID COAGULATION-FACTOR X; STEM-CELLS; NEUTRALIZING ANTIBODIES; GENERATION ADENOVIRUS; INTERNATIONAL-SOCIETY; ONCOLYTIC VIROTHERAPY; GENE-TRANSFER; BINDING SITE; IDENTIFICATION; RECEPTOR AB In adenovirus type 5 (HAdV-5)-derived viral vectors, the fiber protein has been the preferred locale for modifications to alter the natural viral tropism. Hexon, the most abundant capsid protein, has rarely been used for retargeting purposes, likely because the insertion of larger targeting peptides into Hexon often interferes with the assembly of the viral capsid. We previously observed that positively charged molecules enhance the transduction of human multipotent mesenchymal stromal cells (hMSCs) -a cell type of significant interest for clinical development but inefficiently transduced by unmodified HAdV-5-based vectors. As efficient HAdV-5-mediated gene transfer would greatly increase the therapeutic potential of hMSCs, we tested the hypothesis that introducing positively charged amino acids into Hexon might enhance the transduction of hMSCs, enabling efficient expression of selected transgenes. From the constructs that could be rescued as functional virions, one (HAdV-5-HexPos3) showed striking transduction of hMSCs with up to 500-fold increased efficiency. Evaluation of the underlying mechanism identified heparan sulfate proteoglycans (HSPGs) to be essential for virus uptake by the cells. The ease and efficiency of transduction of hMSCs with this vector will facilitate the development of genetically modified hMSCs as therapeutic vehicles in different disciplines, including oncology or regenerative medicine. C1 [Nilson, Robin; Luebbers, Olivia; Kritzinger, Astrid; Kochanek, Stefan; Krutzke, Lea] Univ Ulm, Dept Gene Therapy, Helmholtzstr 8-1, D-89081 Ulm, Baden Wurttembe, Germany. [Schmidt, Christoph Q.] Univ Med Ctr Ulm, Dept Appl Immunol & Immunopharmacol, Ulm, Germany. [Rojewski, Markus; Schrezenmeier, Hubert] Univ Med Ctr Ulm, Inst Transfus Med, Ulm, Germany. [Rojewski, Markus; Schrezenmeier, Hubert] German Red Cross Blood Donat Serv, Inst Clin Transfus Med & Immunogenet Ulm, Ulm, Germany. [Zeplin, Philip Helge] Privatklin Plast & Asthet Chirurg, Schlosspk Klin Ludwigsburg, Ludwigsburg, Germany. [Funk, Wolfgang] Schonheitsklin Dr Funk, Munich, Germany. C3 Ulm University; Ulm University; Ulm University RP Krutzke, L (corresponding author), Univ Ulm, Dept Gene Therapy, Helmholtzstr 8-1, D-89081 Ulm, Baden Wurttembe, Germany. EM Lea.krutzke@uni-ulm.de OI Nilson, Robin/0000-0002-2528-9547; Kochanek, Stefan/0000-0001-7494-1602; Krutzke, Lea/0000-0002-4092-4131 FU German Federal Ministry of Education and Research (BMBF); Federal States of Germany Grant "Innovative Hochschule" [FKZ 3IHS024D]; 7th framework programme of the European Com-mission (project title REBORNE) [241879]; Sanitatsa-kademie der Bundeswehr [E/U2AD/ID018/IF557]; H2020 Programme of the European Commission (project title ADIPOA-2) [643809]; H2020 Societal Challenges Programme [643809] Funding Source: H2020 Societal Challenges Programme FX The authors acknowledge Cornelia Brunner from the University Medical Center Ulmfor providing the HNSCC cell line UM-SCC-11B. The work was supported by the German Federal Ministry of Educa-tion and Research (BMBF) and the Federal States of Germany Grant "Innovative Hochschule" (FKZ 3IHS024D) . Parts of this re-search were funded by the 7th framework programme of the European Com-mission (project title REBORNE, grant agreement number 241879) , the H2020 Programme of the European Commission (project title ADIPOA-2, grant agreement number 643809) , and by the Sanitatsa-kademie der Bundeswehr E/U2AD/ID018/IF557. The materials pre-sented and views expressed here are the responsibility of the authors only. The EU Commission takes no responsibility for any use made of the information set out. 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Dev. PD JUN 9 PY 2022 VL 25 BP 96 EP 110 DI 10.1016/j.omtm.2022.03.004 EA MAR 2022 PG 15 WC Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine GA 0U6SS UT WOS:000787780400010 PM 35402633 OA gold, Green Published DA 2025-10-02 ER PT J AU Dembinski, JL Spaeth, EL Fueyo, J Gomez-Manzano, C Studeny, M Andreeff, M Marini, FC AF Dembinski, J. L. Spaeth, E. L. Fueyo, J. Gomez-Manzano, C. Studeny, M. Andreeff, M. Marini, F. C. TI Reduction of nontarget infection and systemic toxicity by targeted delivery of conditionally replicating viruses transported in mesenchymal stem cells SO CANCER GENE THERAPY LA English DT Article DE gene delivery; fiber-modified adenovirus; MSC; ovarian cancer ID ONCOLYTIC ADENOVIRUS; BONE-MARROW; CELLULAR VEHICLES; PROGENITOR CELLS; OVARIAN-CANCER; GENE-TRANSFER; TUMOR STROMA; TROPISM; MUTANT; DIFFERENTIATION AB The fiber-modified adenoviral vector D-24-RGD (D24RGD) offers vast therapeutic potential. Direct injection of D24RGD has been used to successfully target ovarian tumors in mice. However, systemic toxicity, especially in the liver, profoundly limits the efficacy of direct viral vector delivery. Mesenchymal stem cells (MSC) have the ability to function as a vector for targeted gene therapy because of their preferential engraftment into solid tumors and participation in tumor stroma formation. We show that MSC-guided delivery of D24RGD is specific and efficient and reduces the overall systemic toxicity in mice to negligible levels compared with D24RGD alone. In our model, we found efficient targeted delivery of MSC-D24RGD to both breast and ovarian cell lines. Furthermore, immunohistochemical staining for adenoviral hexon protein confirmed negligible levels of systemic toxicity in mice that were administered MSC-D24RGD compared with those that were administered D24RGD. These data suggest that delivery of D24RGD through MSC not only increases the targeted delivery efficiency, but also reduces the systemic exposure of the virus, thereby reducing overall systemic toxicity to the host and ultimately enhancing its value as an anti-tumor therapeutic candidate. Cancer Gene Therapy (2010) 17, 289-297; doi: 10.1038/cgt.2009.67; published online 30 October 2009 C1 [Dembinski, J. L.; Spaeth, E. L.; Fueyo, J.; Gomez-Manzano, C.; Studeny, M.; Andreeff, M.; Marini, F. C.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Sect Mol Hematol & Therapy, Houston, TX 77030 USA. C3 University of Texas System; UTMD Anderson Cancer Center RP Marini, FC (corresponding author), Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Sect Mol Hematol & Therapy, Box 081,1515 Holcombe Blvd, Houston, TX 77030 USA. EM fmarini@mdanderson.org RI ; Marini, Frank/L-8018-2016; Tuff, Erika/KXR-8177-2024 OI Dembinski, Jennifer/0000-0001-9259-9572; Fueyo, Juan/0000-0001-6941-2335; Spaeth, Erika/0000-0002-5397-3493; Gomez-Manzano, Candelaria/0000-0002-1259-2133 FU NCI NIH HHS [P01 CA055164, P01 CA049639, P50 CA083639, P30 CA016672, RC1 CA146381, P50 CA116199, R01 CA109451] Funding Source: Medline CR Bauerschmitz GJ, 2002, CANCER RES, V62, P1266 Bauerschmitz GJ, 2004, INT J CANCER, V111, P303, DOI 10.1002/ijc.20217 Del Rio M, 2004, GENE THER, V11, pS57, DOI 10.1038/sj.gt.3302370 Devine SM, 2001, EXP HEMATOL, V29, P244, DOI 10.1016/S0301-472X(00)00635-4 EGAN C, 1988, MOL CELL BIOL, V8, P3955, DOI 10.1128/MCB.8.9.3955 Fueyo J, 2000, ONCOGENE, V19, P2, DOI 10.1038/sj.onc.1203251 Fueyo J, 2003, J NATL CANCER I, V95, P652, DOI 10.1093/jnci/95.9.652 Hakkarainen T, 2007, HUM GENE THER, V18, P627, DOI 10.1089/hum.2007.034 Hall B., 2007, V180, P263 Hall B, 2007, INT J HEMATOL, V86, P8, DOI 10.1532/IJH97.06230 Heise C, 2000, NAT MED, V6, P1134, DOI 10.1038/80474 Hemminki A, 2001, MOL THER, V4, P223, DOI 10.1006/mthe.2001.0446 Kanehira M, 2007, CANCER GENE THER, V14, P894, DOI 10.1038/sj.cgt.7701079 Kelly FJ, 2000, CLIN CANCER RES, V6, P4323 Kirn D, 2000, ONCOGENE, V19, P6660, DOI 10.1038/sj.onc.1204094 Komarova S, 2006, MOL CANCER THER, V5, P755, DOI 10.1158/1535-7163.MCT-05-0334 Larochelle A, 2004, SEMIN HEMATOL, V41, P257, DOI 10.1053/j.seminhematol.2004.07.002 Lee K, 2001, MOL THER, V3, P857, DOI 10.1006/mthe.2001.0327 Li S, 2005, GENE THER, V12, P1099, DOI 10.1038/sj.gt.3302505 Liechty KW, 2000, NAT MED, V6, P1282, DOI 10.1038/81395 Nakamizo A, 2005, CANCER RES, V65, P3307, DOI 10.1158/0008-5472.CAN-04-1874 Pereboeva L, 2003, STEM CELLS, V21, P389, DOI 10.1634/stemcells.21-4-389 Roni V, 2003, EXP CELL RES, V287, P28, DOI 10.1016/S0014-4827(03)00133-2 Sonabend AM, 2008, STEM CELLS, V26, P831, DOI 10.1634/stemcells.2007-0758 Spaeth E, 2008, GENE THER, V15, P730, DOI 10.1038/gt.2008.39 Stoff-Khalili MA, 2006, CANCER GENE THER, V13, P606, DOI 10.1038/sj.cgt.7700934 Stolarek R, 2004, CANCER GENE THER, V11, P713, DOI 10.1038/sj.cgt.7700731 Studeny M, 2004, JNCI-J NATL CANCER I, V96, P1593, DOI 10.1093/jnci/djh299 Studeny M, 2002, CANCER RES, V62, P3603 Suzuki K, 2001, CLIN CANCER RES, V7, P120 Tsuda H, 2003, MOL THER, V7, P354, DOI 10.1016/S1525-0016(02)00062-X Wang Y, 2003, MOL CANCER THER, V2, P1233 Yotnda P, 2004, HUM GENE THER, V15, P1229, DOI 10.1089/hum.2004.15.1229 Yu P, 2006, GENE THER, V13, P1131, DOI 10.1038/sj.gt.3302760 NR 34 TC 46 Z9 54 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 EI 1476-5500 J9 CANCER GENE THER JI Cancer Gene Ther. PD APR PY 2010 VL 17 IS 4 BP 289 EP 297 DI 10.1038/cgt.2009.67 PG 9 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 570TJ UT WOS:000275700700007 PM 19876078 OA Green Accepted DA 2025-10-02 ER PT J AU Chastkofsky, MI Pituch, KC Katagi, H Zannikou, M Ilut, L Xiao, T Han, Y Sonabend, AM Curiel, DT Bonner, ER Nazarian, J Horbinski, CM James, CD Saratsis, AM Hashizume, R Lesniak, MS Balyasnikova, I AF Chastkofsky, Michael, I Pituch, Katarzyna C. Katagi, Hiroaki Zannikou, Markella Ilut, Liliana Xiao, Ting Han, Yu Sonabend, Adam M. Curiel, David T. Bonner, Erin R. Nazarian, Javad Horbinski, Craig M. James, C. David Saratsis, Amanda M. Hashizume, Rintaro Lesniak, Maciej S. Balyasnikova, Irina, V TI Mesenchymal Stem Cells Successfully Deliver Oncolytic Virotherapy to Diffuse Intrinsic Pontine Glioma SO CLINICAL CANCER RESEARCH LA English DT Article ID INTRANASAL DELIVERY; EXTENDS SURVIVAL; BRAIN-TUMORS; ADENOVIRUS; EXPRESSION; MUTATIONS; THERAPY; MODEL; REIRRADIATION; MODULATION AB Purpose: Diffuse intrinsic pontine glioma (DIPG) is among the deadliest of pediatric brain tumors. Radiotherapy is the standard-of-care treatment for DIPG, but offers only transient relief of symptoms for patients with DIPG without providing significant survival benefit. Oncolytic virotherapy is an anticancer treatment that has been investigated for treating various types of brain tumors. Experimental Design: Here, we have explored the use of mesenchymal stem cells (MSC) for oncolytic virus (OV) delivery and evaluated treatment efficacy using preclinical models of DIPG. The survivin promoter drives the conditional replication of OV used in our studies. The efficiency of OV entry into the cells is mediated by fiber modification with seven lysine residues (CRAd.S.pK7). Patients' samples and cell lines were analyzed for the expression of viral entry proteins and survivin. The ability of MSCs to deliver OV to DIPG was studied in the context of a low dose of irradiation. Results: Our results show that DIPG cells and tumors exhibit robust expression of cell surface proteins and survivin that enable efficient OV entry and replication in DIPG cells. MSCs loaded with OV disseminate within a tumor and release OV throughout the DIPG brainstem xenografts in mice. Administration of OV-loaded MSCs with radiotherapy to mice bearing brainstem DIPG xenografts results in more prolonged survival relative to that conferred by either therapy alone (P < 0.01). Conclusions: Our study supports OV, CRAd.S.pK7, encapsulated within MSCs as a therapeutic strategy that merits further investigation and potential translation for DIPG treatment. C1 [Chastkofsky, Michael, I; Pituch, Katarzyna C.; Katagi, Hiroaki; Zannikou, Markella; Ilut, Liliana; Xiao, Ting; Han, Yu; Sonabend, Adam M.; Horbinski, Craig M.; James, C. David; Saratsis, Amanda M.; Hashizume, Rintaro; Lesniak, Maciej S.; Balyasnikova, Irina, V] Northwestern Univ, Feinberg Sch Med, Dept Neurol Surg, Chicago, IL 60611 USA. [Curiel, David T.] Washington Univ, Dept Radiat Oncol, St Louis, MO USA. [Bonner, Erin R.; Nazarian, Javad] Childrens Natl Med Ctr, Ctr Genom & Precis Med, Washington, DC 20010 USA. [Bonner, Erin R.] George Washington Univ, Sch Med & Hlth Sci, Inst Biomed Sci, Washington, DC 20052 USA. [Nazarian, Javad] George Washington Univ, Sch Med & Hlth Sci, Dept Integrat Syst Biol, Washington, DC 20052 USA. [Horbinski, Craig M.] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. [Saratsis, Amanda M.] Ann & Robert H Lurie Childrens Hosp Chicago, Div Neurosurg, Dept Pediat Surg, Chicago, IL USA. [Saratsis, Amanda M.; Hashizume, Rintaro] Northwestern Univ, Feinberg Sch Med, Dept Biochem & Mol Genet, Chicago, IL 60611 USA. C3 Northwestern University; Feinberg School of Medicine; Washington University (WUSTL); Children's National Health System; George Washington University; George Washington University; Northwestern University; Feinberg School of Medicine; Ann & Robert H. Lurie Children's Hospital of Chicago; Northwestern University; Feinberg School of Medicine RP Balyasnikova, I (corresponding author), Northwestern Univ, Feinberg Sch Med, 303 E Super St,SQ Room 6-520, Chicago, IL 60611 USA. RI ; XIAO, TING/AAN-8486-2021; curiel, david/KCJ-9827-2024; Han, Yu/GZA-9220-2022 OI Katagi, Hiroaki/0000-0003-3620-9116; XIAO, TING/0000-0002-7502-4395; Sonabend, Adam M/0000-0002-8347-1945; Nazarian, Javad/0000-0002-1951-9828; FU NIH [R01NS087990, R01NS106379, R33 NS101150, P50CA221747]; ORIP of the NIH [P40OD011050]; Northwestern University Flow Cytometry Core Facility - NCI [P30-CA060553]; Center for Advanced Microscopy - NCI [P30-CA060553]; Mouse Histology and Phenotyping Laboratory - NCI [P30-CA060553]; National Cancer Institute [R35CA197725] Funding Source: NIH RePORTER FX This work was supported by NIH R01NS087990, R01NS106379, R33 NS101150, and P50CA221747 SPORE for Translational Approaches to Brain Cancer. We are also grateful to the Nora Redman Endowment Fund of the Community Foundation of Louisville, the IDP Foundation Inc., and to the Isabella Kerr Molina Foundation for generous gifts to support the study. Some of the materials employed in this work were provided by the Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White through a grant from ORIP of the NIH, grant no., P40OD011050. This work was also supported by the Northwestern University Flow Cytometry Core Facility, the Center for Advanced Microscopy, and the Mouse Histology and Phenotyping Laboratory, all supported by NCI P30-CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. The authors are also grateful to the Pathology Core Facility of the Robert H Lurie Comprehensive Cancer Center for its excellent service. 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Cancer Res. PD MAR 15 PY 2021 VL 27 IS 6 BP 1766 EP 1777 DI 10.1158/1078-0432.CCR-20-1499 PG 12 WC Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology GA QY6IV UT WOS:000630142100018 PM 33272983 OA Bronze, Green Submitted DA 2025-10-02 ER PT J AU Mahasa, KJ de Pillis, L Ouifki, R Eladdadi, A Maini, P Yoon, AR Yun, CO AF Mahasa, Khaphetsi Joseph de Pillis, Lisette Ouifki, Rachid Eladdadi, Amina Maini, Philip Yoon, A-Rum Yun, Chae-Ok TI Mesenchymal stem cells used as carrier cells of oncolytic adenovirus results in enhanced oncolytic virotherapy SO SCIENTIFIC REPORTS LA English DT Article ID DRUG-DELIVERY; CANCER CELLS; IMMUNE CELL; TUMOR; VIRUS; THERAPY; GROWTH; NEUROBLASTOMA; ANGIOGENESIS; INHIBITION AB Mesenchymal stem cells (MSCs) loaded with oncolytic viruses are presently being investigated as a new modality of advanced/metastatic tumors treatment and enhancement of virotherapy. MSCs can, however, either promote or suppress tumor growth. To address the critical question of how MSCs loaded with oncolytic viruses affect virotherapy outcomes and tumor growth patterns in a tumor microenvironment, we developed and analyzed an integrated mathematical-experimental model. We used the model to describe both the growth dynamics in our experiments of firefly luciferase-expressing Hep3B tumor xenografts and the effects of the immune response during the MSCs-based virotherapy. We further employed it to explore the conceptual clinical feasibility, particularly, in evaluating the relative significance of potential immune promotive/suppressive mechanisms induced by MSCs loaded with oncolytic viruses. We were able to delineate conditions which may significantly contribute to the success or failure of MSC-based virotherapy as well as generate new hypotheses. In fact, one of the most impactful outcomes shown by this investigation, not inferred from the experiments alone, was the initially counter-intuitive fact that using tumor-promoting MSCs as carriers is not only helpful but necessary in achieving tumor control. Considering the fact that it is still currently a controversial debate whether MSCs exert a pro- or anti-tumor action, mathematical models such as this one help to quantitatively predict the consequences of using MSCs for delivering virotherapeutic agents in vivo. Taken together, our results show that MSC-mediated systemic delivery of oncolytic viruses is a promising strategy for achieving synergistic anti-tumor efficacy with improved safety profiles. C1 [Mahasa, Khaphetsi Joseph] Univ Stellenbosch, DST NRF Ctr Excellence Epidemiol Modelling & Anal, Stellenbosch, South Africa. [Mahasa, Khaphetsi Joseph; Ouifki, Rachid] Univ Pretoria, Dept Math & Appl Math, Pretoria, South Africa. [de Pillis, Lisette] Harvey Mudd Coll, Dept Math, Claremont, CA 91711 USA. [Eladdadi, Amina] Coll St Rose, Dept Math, Albany, NY USA. [Maini, Philip] Univ Oxford, Wolfson Ctr Math Biol, Math Inst, Oxford, England. [Yoon, A-Rum; Yun, Chae-Ok] Hanyang Univ, Coll Engn, Dept Bioengn, Seoul, South Korea. C3 National Research Foundation - South Africa; Stellenbosch University; University of Pretoria; Claremont Colleges; Harvey Mudd College; University of Oxford; Hanyang University RP Mahasa, KJ (corresponding author), Univ Stellenbosch, DST NRF Ctr Excellence Epidemiol Modelling & Anal, Stellenbosch, South Africa.; Mahasa, KJ (corresponding author), Univ Pretoria, Dept Math & Appl Math, Pretoria, South Africa.; Yun, CO (corresponding author), Hanyang Univ, Coll Engn, Dept Bioengn, Seoul, South Korea. EM mahasa@aims.ac.za; chaeok@hanyang.ac.kr RI Yun, Chae-Ok/P-3698-2015; Ouifki, Rachid/A-4064-2017 OI Ouifki, Rachid/0000-0001-7697-1792; dePillis, Lisette/0000-0002-9839-3636; Mahasa, Khaphetsi Joseph/0000-0003-0017-3780 FU National Research Foundation of Korea [2016M3A9B5942352]; Korea Drug Development Fund (KDDF) - MSIP; MOHW, Republic of Korea [KDDF-201904-23]; DST/NRF SARChI Chair in Mathematical Models and Methods in Biosciences and Bioengineering at the University of Pretoria; MOTIE FX This work was supported by grants from the National Research Foundation of Korea (2016M3A9B5942352; Dr. C-O Yun) and Korea Drug Development Fund (KDDF) funded by MSIP, MOTIE, and MOHW [KDDF-201904-23], Republic of Korea; Dr. C-O Yun). K.J.M. and R.O. acknowledge the support from the DST/NRF SARChI Chair in Mathematical Models and Methods in Biosciences and Bioengineering at the University of Pretoria. 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Oncolytic adenoviral virotherapy is an attractive treatment modality for cancer; however, the difficulty remains regarding its intravenous administration. The aim of this study was to develop a targeted therapeutic system which has great potential to overcome the postsurgical residuals and metastasis of HCC. In this system, we developed a conditionally replicative adenovirus (CRAd) loaded on human umbilical cord-derived mesenchymal stem cells (HUMSCs), in which the CRAd contained an adenovirus E1A gene dual regulated by oc-fetoprotein promoter and microRNA-122 target sequence. When HUMSCs homed to the tumor sites and differentiated into hepatocyte-like cells within tumor microenvironment, the CRAds were packaged and released strictly to the local tumor. Subsequently, the CRAd lysed tumor cells selectively with the post-infection regulation. The study showed the specific oncolytic effect of the CRAd to HCC cells and the production of the CRAd by differentiated HUMSCs in vitro. Furthermore, we proved the hepatocyte-like transformation of HUMSC in the microenvironment of orthotopic or heterotopic hepatoma. Finally, this therapeutic system exhibited dramatic tumor inhibition on both orthotopic and subcutaneous hepatic xenograft tumor model mice with less toxicity on normal organs. The study results have demonstrated that this targeted therapeutic strategy is a promising method to resolve the problem of postsurgical residuals and metastasis of HCC. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Yuan, Xiangfei; Zhang, Qing; Zhang, Xiaolong; Bao, Shiqi; Fan, Dongmei; Ru, Yongxin; Dong, Shuxu; Zhang, Yanjun; Xiong, Dongsheng] Chinese Acad Med Sci, Inst Hematol & Hosp Blood Dis, Dept Pharm, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China. [Yuan, Xiangfei; Zhang, Qing; Zhang, Xiaolong; Bao, Shiqi; Fan, Dongmei; Ru, Yongxin; Dong, Shuxu; Zhang, Yanjun; Xiong, Dongsheng] Peking Union Med Coll, Tianjin 300020, Peoples R China. [Yuan, Xiangfei] Nankai Hosp, Tianjin Inst Integrat Med Acute Abdominal Dis, Tianjin 300100, Peoples R China. [Li, Zhenzhen] Xi An Jiao Tong Univ, Affiliated Hosp 2, Natl Local Joint Engn Res Ctr Biodiagnost & Bioth, Xian 710004, Peoples R China. [Zhang, Yizhi; Ye, Zhou] Cent Hosp Karamay, Karamay 834000, Xinjiang, Peoples R China. C3 Chinese Academy of Medical Sciences - Peking Union Medical College; Institute of Hematology & Blood Diseases Hospital - CAMS; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Xi'an Jiaotong University RP Zhang, YJ; Xiong, DS (corresponding author), Chinese Acad Med Sci, Inst Hematol & Hosp Blood Dis, Dept Pharm, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China.; Zhang, YJ; Xiong, DS (corresponding author), Peking Union Med Coll, Tianjin 300020, Peoples R China.; Ye, Z (corresponding author), Cent Hosp Karamay, Karamay 834000, Xinjiang, Peoples R China. EM junjunfriend@126.com; yezhou126@126.com; dsxiong@ihcams.ac.cn RI Zhang, XiaoLong/LDO-6248-2024; fan, dongmei/MVU-0145-2025; Li, zhenzhen/Q-9950-2019 FU National Natural Science Foundation of China [30971291, 81400176, 81572993]; National Science and Technology Major Project [2012zx09102301-015]; China Postdoctoral Science Foundation [2014M560916] FX This work was supported by the National Natural Science Foundation of China (Grant Nos. 30971291, 81400176, 81572993), National Science and Technology Major Project (Grant No. 2012zx09102301-015), and China Postdoctoral Science Foundation (Grant No.2014M560916). 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Oncolytic immunotherapy with engineered adenoviruses (OAd) may disrupt the TME by infecting tumor cells, as well as surrounding stroma, to improve the functionality of tumor-directed chimeric antigen receptor (CAR)-T cells, yet efficient delivery of OAds to solid tumors has been challenging. Here we describe how mesenchymal stromal cells (MSCs) can be used to systemically deliver a binary vector containing an OAd together with a helper-dependent Ad (HDAd; combinatorial Ad vector [CAd]) that expresses interleukin-12 (IL-12) and checkpoint PD-L1 (programmed death-ligand 1) blocker. CAdinfected MSCs deliver and produce functional virus to infect and lyse lung tumor cells while stimulating CAR-T cell anti-tumor activity by release of IL-12 and PD-L1 blocker. The combination of this approach with administration of HER.2-specific CAR-T cells eliminates 3D tumor spheroids in vitro and suppresses tumor growth in two orthotopic lung cancer models in vivo. Treatment with CAd MSCs increases the overall numbers of human T cells in vivo compared to CAR-T cell only treatment and enhances their polyfunctional cytokine secretion. These studies combine the predictable targeting of CAR-T cells with the advantages of cancer cell lysis and TME disruption by systemic MSC delivery of oncolytic virotherapy: incorporation of immunostimulation by cytokine and checkpoint inhibitor production through the HDAd further enhances anti-tumor activity. C1 [McKenna, Mary K.; Englisch, Alexander; Brenner, Benjamin; Smith, Tyler; Hoyos, Valentina; Suzuki, Masataka; Brenner, Malcolm K.] Baylor Coll Med, Houston Methodist Hosp, Texas Childrens Hosp, Ctr Cell Gene Therapy, Houston, TX 77030 USA. [Englisch, Alexander] Univ Childrens Hosp Muenster, Dept Pediat Hematol & Oncol, Munster, Germany. [Brenner, Benjamin] Northwestern Univ, Dept Biomed Engn, 2145 Sheridan Rd, Evanston, IL 60208 USA. [Hoyos, Valentina] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Suzuki, Masataka] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. C3 Houston Methodist; Baylor College of Medicine; Baylor College Medical Hospital; University of Munster; Northwestern University; Baylor College of Medicine; Baylor College of Medicine RP Brenner, MK (corresponding author), Baylor Coll Med, Houston Methodist Hosp, Texas Childrens Hosp, Ctr Cell Gene Therapy, Houston, TX 77030 USA. EM mbrenner@bcm.edu RI ; Brenner, Malcolm/Y-2509-2019 OI McKenna, Katie/0000-0002-2357-1733; FU Integrated Microscopy Core at Baylor College of Medicine; NIH [DK56338, CA125123]; CPRIT [RP150578, RP170719]; Dan L. Duncan Comprehensive Cancer Center; John S. Dunn Gulf Coast Consortium for Chemical Genomics; NCI [P30 CA125123]; National Heart, Lung, and Blood Institute of The National Institutes of Health [5T32HL092332-17]; National Cancer Institute [5PO1CA094237-15] FX Imaging for this project was supported by the Integrated Microscopy Core at Baylor College of Medicine with funding from NIH (DK56338 and CA125123), CPRIT (RP150578 and RP170719), the Dan L. Duncan Comprehensive Cancer Center, and the John S. Dunn Gulf Coast Consortium for Chemical Genomics. The authors extend special thanks to Ms. Hannah Johnson with the Integrated Microscopy Core. The authors thank the Baylor College of Medicine Pathology Core (HTAP) and Dr. Patricia Castro for performing immunohistochemistry and H&E staining for tissue microarray slides supported by NCI award P30 CA125123. The authors thank Dr. Reid Powell with Texas A&M Center for Advanced Imaging for image analysis. The authors are grateful to Ms. Catherine Gillespie for editing the manuscript. This project was supported by the National Heart, Lung, and Blood Institute of The National Institutes of Health under award number 5T32HL092332-17 to Principal Investigator: Dr. Helen Heslop and The National Cancer Institute under the award 5PO1CA094237-15. 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PD MAY 5 PY 2021 VL 29 IS 5 BP 1808 EP 1820 DI 10.1016/j.ymthe.2021.02.004 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA RY1EZ UT WOS:000647661000015 PM 33571680 OA Bronze, Green Submitted DA 2025-10-02 ER PT J AU Yin, L Liu, XT Shi, YH Ocansey, DKW Hu, YY Li, XX Zhang, CX Xu, WR Qian, H AF Yin, Lei Liu, Xiaotian Shi, Yinghong Ocansey, Dickson Kofi Wiredu Hu, Yuyan Li, Xiaoxi Zhang, Chenxiao Xu, Wenrong Qian, Hui TI Therapeutic Advances of Stem Cell-Derived Extracellular Vesicles in Regenerative Medicine SO CELLS LA English DT Review DE stem cell; extracellular vesicle; tissue damage; regenerative medicine ID MESENCHYMAL STROMAL CELLS; FUNCTIONAL RECOVERY; ONCOLYTIC ADENOVIRUS; CARDIAC-FUNCTION; LUNG INJURY; EXOSOMES; DELIVERY; REPAIR; MICROVESICLES; GROWTH AB Extracellular vesicles (EVs), which are the main paracrine components of stem cells, mimic the regenerative capacity of these cells. Stem cell-derived EVs (SC-EVs) have been used for the treatment of various forms of tissue injury in preclinical trials through maintenance of their stemness, induction of regenerative phenotypes, apoptosis inhibition, and immune regulation. The efficiency of SC-EVs may be enhanced by selecting the appropriate EV-producing cells and cell phenotypes, optimizing cell culture conditions for the production of optimal EVs, and further engineering the EVs produced to transport therapeutic and targeting molecules. C1 [Yin, Lei; Liu, Xiaotian; Shi, Yinghong; Ocansey, Dickson Kofi Wiredu; Hu, Yuyan; Li, Xiaoxi; Zhang, Chenxiao; Xu, Wenrong; Qian, Hui] Jiangsu Univ, Zhenjiang Key Lab High Technol Res Exosomes Fdn &, Sch Med, Jiangsu Key Lab Med Sci & Lab Med, 301 Xuefu Rd, Zhenjiang 212013, Jiangsu, Peoples R China. C3 Jiangsu University RP Xu, WR; Qian, H (corresponding author), Jiangsu Univ, Zhenjiang Key Lab High Technol Res Exosomes Fdn &, Sch Med, Jiangsu Key Lab Med Sci & Lab Med, 301 Xuefu Rd, Zhenjiang 212013, Jiangsu, Peoples R China. EM yinl1882@163.com; lxt18796026236@163.com; shiwuyisunny@163.com; dickson.ocansey@ucc.edu.gh; 13777884048@163.com; xiaoxili2010@163.com; z565788379@163.com; icls@ujs.edu.cn; lstmmmlst@163.com RI Ocansey, Dickson WK/AAO-5984-2020; Ocansey, Dickson/AAO-5984-2020; SHI, YH/HLG-1159-2023 OI Ocansey, Dickson WK/0000-0003-3547-0857; Qian, Hui/0000-0002-0098-3196; Yin, Lei/0000-0003-3316-694X FU National Natural Science Foundation of China [81871496]; Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application [SS-2018003]; Innovation Project for Graduate Student Research of Jiangsu Province [KYCX17_1819]; Technology Development Project of Jiangsu University [20180361]; Priority Academic Program Development of Jiangsu Higher Education Institutions (Phase III) FX This work was supported by the National Natural Science Foundation of China (Grant 81871496), Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application (Grant SS-2018003), and Innovation Project for Graduate Student Research of Jiangsu Province (Grant KYCX17_1819), Technology Development Project of Jiangsu University (20180361), and Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (Phase III). 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MDPI PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND EI 2073-4409 J9 CELLS-BASEL JI Cells PD MAR PY 2020 VL 9 IS 3 AR 707 DI 10.3390/cells9030707 PG 28 WC Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology GA LI2TV UT WOS:000529337400184 PM 32183102 OA Green Published, gold DA 2025-10-02 ER PT J AU Kavari, SL Shah, K AF Kavari, Sanam L. Shah, Khalid TI Concise Review: Engineered Stem Cells Targeting Multiple Cell Surface Receptors in Tumors SO STEM CELLS LA English DT Review DE Adult stem cells; Cell surface receptors; Cancer; Signal transduction; Cell death ID MESENCHYMAL STROMAL CELLS; INTERFERON-BETA GENE; ONCOLYTIC ADENOVIRUS; THERAPEUTIC-EFFICACY; TRAIL EXPRESSION; GLIOMA-CELLS; CANCER-CELLS; IFN-BETA; BRAIN; MIGRATION AB Multiple stem cell types exhibit inherent tropism for cancer, and engineered stem cells have been used as therapeutic agents to specifically target cancer cells. Recently, stem cells have been engineered to target multiple surface receptors on tumor cells, as well as endothelial and immune cells in the tumor microenvironment. In this review, we discuss the rationales and strategies for developing multiple receptor-targeted stem cells, their mechanisms of action, and the promises and challenges they hold as cancer therapeutics. Stem Cells 2019 C1 [Kavari, Sanam L.; Shah, Khalid] Harvard Med Sch, Brigham & Womens Hosp, Ctr Stem Cell Therapeut & Imaging CSTI, Boston, MA 02115 USA. [Kavari, Sanam L.; Shah, Khalid] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Shah, Khalid] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University RP Shah, K (corresponding author), Harvard Med Sch, Brigham & Womens Hosp, Ctr Stem Cell Therapeut & Imaging CSTI, Boston, MA 02115 USA. EM kshah@bwh.harvard.edu RI Shah, Amy/AAB-4631-2020 OI Kavari, Sanam L/0000-0002-1224-733X FU NIH [R01-CA201148, R01-NS107857] FX This work was supported by NIH grants R01-CA201148 (K.S.) and R01-NS107857 (K.S.). 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McFadden, Grant Fidyk, Wojciech Chmielik, Ewa Pazdzior, Marlena Grajek, Maciej Kozik, Violetta Sochanik, Aleksander TI Myxoma Virus Expressing LIGHT (TNFSF14) Pre-Loaded into Adipose-Derived Mesenchymal Stem Cells Is Effective Treatment for Murine Pancreatic Adenocarcinoma SO CANCERS LA English DT Article DE adipose tissue-derived stem cells (ADSCs); mesenchymal stem cells; oncolytic virus; myxoma virus; oncolytic virotherapy; pancreatic ductal adenocarcinoma AB Simple Summary Pancreatic cancer is a deadly disease with no effective therapy. Oncolytic viruses such as myxoma (MYXV) have revealed great potential to treat malignancies, due to dual anti-cancer effects-oncolytic and immune-stimulating effects. We aimed to verify whether adipose-derived mesenchymal stem cells (ADSCs) pre-loaded ex vivo with transgene-armed myxoma construct would be useful for transferring the virus to murine pancreatic lesions and whether this would reduce tumor burden. We confirmed that the carrier cells remained viable after infection, in contrast to pancreatic cancer cells, which were destroyed. Intraperitoneal (IP) administration of the shielded virus (ADSCs/MYXV) revealed localization in the pancreas, decreased tumor burden and an adaptive anti-tumor immune response. We conclude that ADSCs pre-loaded with recombinant MYXV and administered IP allowed for the ferrying of the virus to pancreatic cancer lesions, followed by tumor regression and extended survival in the treated mice. This therapeutic approach has excellent potential for treating pancreatic cancer. Pancreatic ductal adenocarcinoma (PDAC) is a weakly immunogenic fatal neoplasm. Oncolytic viruses with dual anti-cancer properties-oncolytic and immune response-boosting effects-have great potential for PDAC management. Adipose-derived stem cells (ADSCs) of mesenchymal origin were infected ex vivo with recombinant myxoma virus (MYXV), which encodes murine LIGHT, also called tumor necrosis factor ligand superfamily member 14 (TNFSF14). The viability and proliferation of ADSCs were not remarkably decreased (1-2 days) following MYXV infection, in sharp contrast to cells of pancreatic carcinoma lines studied, which were rapidly killed by the infection. Comparison of the intraperitoneal (IP) vs. the intravenous (IV) route of ADSC/MYXV administration revealed more pancreas-targeted distribution of the virus when ADSCs were delivered IP to mice bearing orthotopically injected PDAC. The biodistribution, tumor burden reduction and anti-tumor adaptive immune response were examined. Bioluminescence data, used to assess the presence of the luciferase-tagged virus after IP injection, indicated enhanced trafficking into the pancreata of mice bearing orthotopically-induced PDAC, as compared to tumor-free animals, resulting in extended survival of the treated PDAC-seeded animals and in the boosted expression of key adaptive immune response markers. We conclude that ADSCs pre-loaded with transgene-armed MYXV and administered IP allow for the effective ferrying of the oncolytic virus to sites of PDAC and mediate improved tumor regression. C1 [Jazowiecka-Rakus, Joanna; Hadrys, Agata; Pazdzior, Marlena; Sochanik, Aleksander] Maria Sklodowska Curie Natl Res Inst Oncol, Ctr Translat Res & Mol Biol Canc, Gliwice Branch, Wybrzeze AK 15, PL-44102 Gliwice, Poland. [Hadrys, Agata; Pazdzior, Marlena; Kozik, Violetta] Univ Silesia, Inst Chem, Szkolna 9, PL-40007 Katowice, Poland. [Rahman, Masmudur M.; McFadden, Grant] Arizona State Univ, Biodesign Inst, Tempe, AZ 85287 USA. [Fidyk, Wojciech] Maria Sklodowska Curie Natl Res Inst Oncol, Gliwice Branch, Dept Bone Marrow Transplantat & Hematol Oncol, Wybrzeze AK 15, PL-44102 Gliwice, Poland. [Chmielik, Ewa] Maria Sklodowska Curie Natl Res Inst Oncol, Tumor Pathol Dept, Gliwice Branch, Wybrzeze AK 15, PL-44102 Gliwice, Poland. [Grajek, Maciej] Maria Sklodowska Curie Natl Res Inst Oncol, Oncol & Reconstruct Surg Dept, Gliwice Branch, Wybrzeze AK 15, PL-44102 Gliwice, Poland. C3 University of Silesia in Katowice; Arizona State University; Arizona State University-Tempe RP Jazowiecka-Rakus, J (corresponding author), Maria Sklodowska Curie Natl Res Inst Oncol, Ctr Translat Res & Mol Biol Canc, Gliwice Branch, Wybrzeze AK 15, PL-44102 Gliwice, Poland. EM Joanna.Jazowiecka@io.gliwice.pl; Agata.Hadrys@io.gliwice.pl; Masmudur.Rahman@asu.edu; grantmcf@asu.edu; Wojciech.Fidyk@io.gliwice.pl; Ewa.Chmielik@io.gliwice.pl; Marlena.Pazdzior@io.gliwice.pl; Maciej.Grajek@io.gliwice.pl; violetta.kozik@us.edu.pl; Aleksander.Sochanik@io.gliwice.pl RI ; Fidyk, Wojciech/X-1469-2018 OI McFadden, Grant/0000-0002-2556-3526; Kawulok, Agata/0000-0002-3315-428X; Sochanik, Aleksander/0000-0003-2674-246X; Fidyk, Wojciech/0000-0002-5953-7131; Pazdzior-Heiske, Marlena/0000-0002-8631-8663; Rahman, Masmudur Mohammed/0000-0002-7177-819X; Chmielik, Ewa/0000-0001-8316-0541; Jazowiecka-Rakus, Joanna/0000-0001-5558-6115 FU National Science Centre, Poland [2016/22/M/NZ6/00418]; DNAtrix FX This research was funded by National Science Centre, Poland, grant number 2016/22/M/NZ6/00418. The construction of vMyx-mLIGHT-Fluc/tdTr was funded by a Sponsored Research Agreement (SRA) from DNAtrix. 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Zaidan, Nada TI Oncolytic Herpes Simplex Virus-Based Therapies for Cancer SO CELLS LA English DT Review DE oncolytic herpes simplex virus (oHSV); virotherapy; immunotherapy; cancer ID MESENCHYMAL STEM-CELLS; TALIMOGENE LAHERPAREPVEC; ANTITUMOR-ACTIVITY; SYSTEMIC DELIVERY; CLINICAL-TRIALS; STROMAL CELLS; EFFICACY; MUTANT; REPLICATION; IMMUNITY AB With the increased worldwide burden of cancer, including aggressive and resistant cancers, oncolytic virotherapy has emerged as a viable therapeutic option. Oncolytic herpes simplex virus (oHSV) can be genetically engineered to target cancer cells while sparing normal cells. This leads to the direct killing of cancer cells and the activation of the host immunity to recognize and attack the tumor. Different variants of oHSV have been developed to optimize its antitumor effects. In this review, we discuss the development of oHSV, its antitumor mechanism of action and the clinical trials that have employed oHSV variants to treat different types of tumor. C1 [Aldrak, Norah; Alsaab, Sarah; Algethami, Aliyah; Alomary, Mohammad N.; Zaidan, Nada] King Abdulaziz City Sci & Technol, Ctr Excellence Biomed, Joint Ctr Excellence Program, POB 6086, Riyadh 11451, Saudi Arabia. [Alsaab, Sarah; Alomary, Mohammad N.; Zaidan, Nada] King Abdulaziz City Sci & Technol, Natl Biotechnol Ctr, Life Sci & Environm Res Inst, POB 6086, Riyadh 11451, Saudi Arabia. [Bhere, Deepak; Wakimoto, Hiroaki; Shah, Khalid] Harvard Med Sch, Brigham & Womens Hosp, Ctr Stem Cell Therapeut & Imaging CSTI, Boston, MA 02115 USA. [Bhere, Deepak; Wakimoto, Hiroaki; Shah, Khalid] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Bhere, Deepak; Wakimoto, Hiroaki; Shah, Khalid] Harvard Med Sch, Brigham & Womens Hosp, BWH Ctr Excellence Biomed, Boston, MA 02115 USA. Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Wakimoto, Hiroaki] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. C3 Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University RP Alomary, MN; Zaidan, NA (corresponding author), King Abdulaziz City Sci & Technol, Ctr Excellence Biomed, Joint Ctr Excellence Program, POB 6086, Riyadh 11451, Saudi Arabia.; Alomary, MN; Zaidan, NA (corresponding author), King Abdulaziz City Sci & Technol, Natl Biotechnol Ctr, Life Sci & Environm Res Inst, POB 6086, Riyadh 11451, Saudi Arabia. EM Naldrak@kacst.edu.sa; smalsaab@kacst.edu.sa; asalgethami@kacst.edu.sa; DBHERE@BWH.HARVARD.EDU; HWAKIMOTO@mgh.harvard.edu; KSHAH@bwh.harvard.edu; malomary@kacst.edu.sa; nzaidan@kacst.edu.sa RI Alomary, Mohammad/AAH-5788-2019; Wakimoto, Hiroaki/H-4533-2019; Bhere, Deepak/Y-7603-2019 OI Aldrak, Norah Abdulrahman/0000-0002-6966-0395; Bhere, Deepak/0000-0003-4142-5518; Alomary, Mohammad/0000-0001-7909-4377; Wakimoto, Hiroaki/0000-0001-8225-241X FU King Abdulaziz City for Science and Technology (KACST) through the Center of Excellence for Biomedicine (CEBM) FX This work was supported by a grant from King Abdulaziz City for Science and Technology (KACST) through the Center of Excellence for Biomedicine (CEBM). 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Gentschev, Ivaylo Nolte, Ingo Ogilvie, Gregory Szalay, Aladar A. TI Oncolytic virotherapy in veterinary medicine: current status and future prospects for canine patients SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Review DE cancer; canine cancer therapy; oncolytic virus; oncolysis; target molecule; combination therapy ID ENDOTHELIAL GROWTH-FACTOR; REPLICATION-COMPETENT ADENOVIRUS; THYMIDINE KINASE-ACTIVITY; MESENCHYMAL STEM-CELLS; VACCINIA VIRUS; ANTITUMOR-ACTIVITY; IMMUNOHISTOCHEMICAL EXPRESSION; INTRATUMORAL SPREAD; MALIGNANT-LYMPHOMA; SYSTEMIC DELIVERY AB Oncolytic viruses refer to those that are able to eliminate malignancies by direct targeting and lysis of cancer cells, leaving non-cancerous tissues unharmed. Several oncolytic viruses including adenovirus strains, canine distemper virus and vaccinia virus strains have been used for canine cancer therapy in preclinical studies. However, in contrast to human studies, clinical trials with oncolytic viruses for canine cancer patients have not been reported. An 'ideal' virus has yet to be identified. This review is focused on the prospective use of oncolytic viruses in the treatment of canine tumors - a knowledge that will undoubtedly contribute to the development of oncolytic viral agents for canine cancer therapy in the future. C1 [Patil, Sandeep S.; Gentschev, Ivaylo; Szalay, Aladar A.] Univ Wurzburg, Dept Biochem, D-97074 Wurzburg, Germany. [Gentschev, Ivaylo; Szalay, Aladar A.] Genelux Corp, San Diego Sci Ctr, San Diego, CA USA. [Nolte, Ingo] Univ Vet Med, Small Anim Clin, D-30173 Hannover, Germany. [Ogilvie, Gregory] Calif Vet Specialists, Angel Care Canc Ctr, Carlsbad, CA 92008 USA. [Ogilvie, Gregory; Szalay, Aladar A.] Univ Calif San Diego, Dept Radiat Oncol, Moores Canc Ctr, La Jolla, CA 92093 USA. [Szalay, Aladar A.] Univ Wurzburg, Rudolf Virchow Ctr Expt Biomed, D-97078 Wurzburg, Germany. [Szalay, Aladar A.] Univ Wurzburg, Inst Mol Infect Biol, D-97078 Wurzburg, Germany. C3 University of Wurzburg; Genelux Corporation; University of Veterinary Medicine Hannover; University of California System; University of California San Diego; University of Wurzburg; University of Wurzburg RP Szalay, AA (corresponding author), Univ Wurzburg, Dept Biochem, D-97074 Wurzburg, Germany. EM aaszalay@genelux.com RI ; Gentschev, Ivaylo/AAJ-5819-2021 OI Ogilvie, Gina/0000-0001-5783-4493; FU Genelux Corporation, San Diego, USA; German Excellence Initiative to the Graduate School of Life Sciences, University of Wuerzburg; German Research Foundation (DFG); University of Wuerzburg FX We like to thank J. Stritzker, Q. Zhang, N. G. Chen, Y. A. Yu and A. MacNeill for providing unpublished data to the authors and J. Stritzker, D. Haddad and B. Minev for critical reading of the manuscript. The original studies of I. Gentschev, I. Nolte and A.A. Szalay presented in this review were funded by Genelux Corporation, San Diego, USA. S. S. Patil is a graduate fellow and supported by a grant of the German Excellence Initiative to the Graduate School of Life Sciences, University of Wuerzburg. This publication was funded by the German Research Foundation (DFG) and the University of Wuerzburg in the funding programme Open Access Publishing. 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Transl. Med. PD JAN 4 PY 2012 VL 10 AR 3 DI 10.1186/1479-5876-10-3 PG 10 WC Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine GA 901IB UT WOS:000300957000002 PM 22216938 OA Green Submitted, gold DA 2025-10-02 ER PT J AU Pol, J Buque, A Aranda, F Bloy, N Cremer, I Eggermont, A Erbs, P Fucikova, J Galon, J Limacher, JM Preville, X Sautes-Fridman, C Spisek, R Zitvogel, L Kroemer, G Galluzzi, L AF Pol, Jonathan Buque, Aitziber Aranda, Fernando Bloy, Norma Cremer, Isabelle Eggermont, Alexander Erbs, Philippe Fucikova, Jitka Galon, Jerome Limacher, Jean-Marc Preville, Xavier Sautes-Fridman, Catherine Spisek, Radek Zitvogel, Laurence Kroemer, Guido Galluzzi, Lorenzo TI Trial Watch-Oncolytic viruses and cancer therapy SO ONCOIMMUNOLOGY LA English DT Review DE Cavatak (TM); GM-CSF; JX-594; ONCOS-102; Reolysin (R); talimogene laherparepvec ID VESICULAR STOMATITIS-VIRUS; PHASE-I TRIAL; COLONY-STIMULATING FACTOR; NEWCASTLE-DISEASE VIRUS; LAHERPAREPVEC T-VEC; IMMUNOTHERAPEUTIC VACCINIA VIRUS; POTENT ANTITUMOR-ACTIVITY; HUMAN COLORECTAL-CANCER; MESENCHYMAL STEM-CELLS; HERPES-SIMPLEX VIRUS-1 AB Oncolytic virotherapy relies on the administration of non-pathogenic viral strains that selectively infect and kill malignant cells while favoring the elicitation of a therapeutically relevant tumor-targeting immune response. During the past few years, great efforts have been dedicated to the development of oncolytic viruses with improved specificity and potency. Such an intense wave of investigation has culminated this year in the regulatory approval by the US Food and Drug Administration (FDA) of a genetically engineered oncolytic viral strain for use in melanoma patients. Here, we summarize recent preclinical and clinical advances in oncolytic virotherapy. C1 [Pol, Jonathan; Buque, Aitziber; Bloy, Norma; Cremer, Isabelle; Galon, Jerome; Sautes-Fridman, Catherine; Kroemer, Guido; Galluzzi, Lorenzo] INSERM, U1138, Paris, France. [Pol, Jonathan; Buque, Aitziber; Bloy, Norma; Cremer, Isabelle; Galon, Jerome; Sautes-Fridman, Catherine; Kroemer, Guido; Galluzzi, Lorenzo] Univ Paris 05, Sorbonne Paris Cite, Paris, France. [Pol, Jonathan; Buque, Aitziber; Bloy, Norma; Cremer, Isabelle; Galon, Jerome; Sautes-Fridman, Catherine; Kroemer, Guido; Galluzzi, Lorenzo] Univ Paris 06, Paris, France. [Pol, Jonathan; Buque, Aitziber; Bloy, Norma; Kroemer, Guido; Galluzzi, Lorenzo] Ctr Rech Cordeliers, Equipe Labellisee Ligue Natl Canc 11, Paris, France. [Pol, Jonathan; Buque, Aitziber; Bloy, Norma; Eggermont, Alexander; Zitvogel, Laurence; Galluzzi, Lorenzo] Gustave Roussy Canc Campus, Villejuif, France. [Aranda, Fernando] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Grp Immune Receptors Innate & Adapt Syst, Barcelona, Spain. [Cremer, Isabelle; Sautes-Fridman, Catherine] Ctr Rech Cordeliers, Equipe 13, Paris, France. [Erbs, Philippe; Limacher, Jean-Marc; Preville, Xavier] Transgene SA, Illkirch Graffenstaden, France. [Fucikova, Jitka; Spisek, Radek] Sotio, Prague, Czech Republic. [Fucikova, Jitka; Spisek, Radek] Charles Univ Prague, Dept Immunol, Fac Med 2, Prague, Czech Republic. [Fucikova, Jitka; Spisek, Radek] Charles Univ Prague, Univ Hosp Motol, Prague, Czech Republic. [Galon, Jerome] Ctr Rech Cordeliers, Lab Integrat Canc Immunol, Paris, France. [Zitvogel, Laurence] INSERM, U1015, CICBT507, Villejuif, France. [Kroemer, Guido] Hop Europeen Georges Pompidou, AP HP, Pole Biol, Paris, France. [Kroemer, Guido] Gustave Roussy Canc Campus, Metabol & Cell Biol Platforms, Villejuif, France. [Kroemer, Guido] Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Stockholm, Sweden. C3 Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Universite Paris Cite; Sorbonne Universite; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Sorbonne Universite; UNICANCER; Gustave Roussy; University of Barcelona; Hospital Clinic de Barcelona; IDIBAPS; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Sorbonne Universite; Transgene SA; Motol University Hospital; Charles University Prague; Motol University Hospital; Charles University Prague; Universite Paris Cite; Sorbonne Universite; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Saclay; Institut National de la Sante et de la Recherche Medicale (Inserm); Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Europeen Georges-Pompidou - APHP; UNICANCER; Gustave Roussy; Karolinska Institutet; Karolinska University Hospital RP Kroemer, G; Galluzzi, L (corresponding author), INSERM, U1138, Paris, France.; Kroemer, G; Galluzzi, L (corresponding author), Univ Paris 05, Sorbonne Paris Cite, Paris, France.; Kroemer, G; Galluzzi, L (corresponding author), Univ Paris 06, Paris, France.; Kroemer, G; Galluzzi, L (corresponding author), Ctr Rech Cordeliers, Equipe Labellisee Ligue Natl Canc 11, Paris, France.; Galluzzi, L (corresponding author), Gustave Roussy Canc Campus, Villejuif, France.; Kroemer, G (corresponding author), Hop Europeen Georges Pompidou, AP HP, Pole Biol, Paris, France.; Kroemer, G (corresponding author), Gustave Roussy Canc Campus, Metabol & Cell Biol Platforms, Villejuif, France.; Kroemer, G (corresponding author), Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Stockholm, Sweden. EM kroemer@orange.fr; deadoc@vodafone.it RI Erbs, Philippe/HGV-1513-2022; Kroemer, Guido/B-4263-2013; Eggermont, Alexander/ACQ-5262-2022; Sautes-Fridman, Catherine/JOZ-3968-2023; sautes-fridman, catherine/JOZ-3968-2023; KROEMER, Guido/B-4263-2013; Cremer, Isabelle/D-4278-2017; Pol, Jonathan/R-6507-2016; Buque, Aitziber/D-8231-2012; Aranda, Fernando/N-2112-2014; Galon, Jerome/G-9838-2019; Aranda, Fernando/N-9649-2019; Galluzzi, Lorenzo/AAG-6432-2019 OI Kroemer, Guido/0000-0002-9334-4405; Pol, Jonathan/0000-0002-8355-7562; , Aitziber/0000-0002-7698-8778; ZITVOGEL, laurence/0000-0003-1596-0998; sautes-fridman, catherine/0000-0003-1735-8722; Cremer, Isabelle/0000-0002-0963-1031; Aranda, Fernando/0000-0002-9364-474X; Galon, Jerome/0000-0001-9635-1339; Erbs, Philippe/0000-0002-6810-4610; Preville, Xavier/0000-0002-1416-7405; FU Ligue contre le Cancer (equipe labelisee); Agence National de la Recherche (ANR); Association pour la recherche sur le cancer (ARC); Canceropole Ile-de-France; AXA Chair for Longevity Research; Institut National du Cancer (INCa); Fondation Bettencourt-Schueller; Fondation de France; Fondation pour la Recherche Medicale (FRM); European Commission (ArtForce); European Research Council (ERC); LabEx Immuno-Oncology; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); SIRIC Cancer Research and Personalized Medicine (CARPEM); Paris Alliance of Cancer Research Institutes (PACRI) FX Authors are supported by the Ligue contre le Cancer (equipe labelisee); Agence National de la Recherche (ANR); Association pour la recherche sur le cancer (ARC); Canceropole Ile-de-France; AXA Chair for Longevity Research; Institut National du Cancer (INCa); Fondation Bettencourt-Schueller; Fondation de France; Fondation pour la Recherche Medicale (FRM); the European Commission (ArtForce); the European Research Council (ERC); the LabEx Immuno-Oncology; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); and the Paris Alliance of Cancer Research Institutes (PACRI). 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WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2016 VL 5 IS 2 AR e1117740 DI 10.1080/2162402X.2015.1117740 PG 15 WC Oncology; Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Immunology GA DI3FW UT WOS:000373385000046 PM 27057469 OA gold, Green Submitted DA 2025-10-02 ER PT J AU Sonabend, AM Ulasov, IV Tyler, MA Rivera, AA Mathis, JM Lesniak, MS AF Sonabend, Adam M. Ulasov, Ilya V. Tyler, Matthew A. Rivera, Angel A. Mathis, James M. Lesniak, Maciej S. TI Mesenchymal stem cells effectively deliver an oncolytic adenovirus to intracranial glioma SO STEM CELLS LA English DT Article DE glioma; stem cells; adenovirus; oncolytic virus; vector; migration; gene therapy ID HUMAN BONE-MARROW; GENE-TRANSFER; SURVIVIN PROMOTER; MALIGNANT GLIOMA; IN-VITRO; THERAPY; REPLICATION; MIGRATION; VECTORS; EXPRESSION AB Gene therapy represents a promising treatment alternative for patients with malignant gliomas. Nevertheless, in the setting of these highly infiltrative tumors, transgene delivery remains a challenge. Indeed, viral vehicles tested in clinical trials often target only those tumor cells that are adjacent to the injection site. In this study, we examined the feasibility of using human mesenchymal stem cells (hMSC) to deliver a replication-competent oncolytic adenovirus (CRAd) in a model of intracranial malignant glioma. To do so, CRAds with a chimeric 5/3 fiber or RGD backbone with or without CXCR4 promoter driving E1A were examined with respect to replication and toxicity in hMSC, human astrocytes, and the human glioma cell line U87MG by quantitative polymerase chain reaction and membrane integrity assay. CRAd delivery by virus-loaded hMSC was then evaluated in vitro and in an in vivo model of mice bearing intracranial U87MG xenografts. Our results show that hMSC are effectively infected by CRAds that use the CXCR4 promoter. CRAd-CXCR4-RGD had the highest replication, followed by CRAd-CXCR4-5/3, in hMSC, with comparable levels of toxicity. In U87MG tumor cells, CRAdCXCR4 -5/3 showed the highest replication and toxicity. Virus-loaded hMSC effectively migrated in vitro and released CRAds that infected U87MG glioma cells. When injected away from the tumor site in vivo, hMSC migrated to the tumor and delivered 46-fold more viral copies than injection of CRAd-CXCR4-5/3 alone. Taken together, these results indicate that hMSC migrate and deliver CRAd to distant glioma cells. This delivery strategy should be explored further, as it could improve the outcome of oncolytic virotherapy for glioma. C1 [Sonabend, Adam M.; Ulasov, Ilya V.; Tyler, Matthew A.; Lesniak, Maciej S.] Univ Chicago, Brain Tumor Ctr, Chicago, IL 60637 USA. [Rivera, Angel A.] Univ Alabama Birmingham, Div Human Gene Therapy, Birmingham, AL USA. [Mathis, James M.] Louisiana Hlth Sci Ctr, Dept Cellular Biol & Anat, Shreveport, LA USA. C3 University of Chicago; University of Alabama System; University of Alabama Birmingham; Louisiana State University System; Louisiana State University Health Sciences Center at Shreveport RP Lesniak, MS (corresponding author), Univ Chicago, Neurosurg Sect, 5841 S Maryland Ave,MC 3026, Chicago, IL 60637 USA. EM mlesniak@surgery.bsd.uchicago.edu RI Ulasov, Ilya/A-2352-2014; Mathis, J. Michael/J-1379-2018; Mathis, J./J-1379-2018; Rivera, Ángel/GRJ-2093-2022 OI Ulasov, Ilya/0000-0002-0818-0363; Mathis, J. Michael/0000-0001-5528-5195; FU NINDS NIH HHS [K08-NS046430] Funding Source: Medline CR ANNEGERS JF, 1981, ARCH NEUROL-CHICAGO, V38, P217, DOI 10.1001/archneur.1981.00510040043006 Banerjee NS, 2004, MOL CANCER THER, V3, P437 Bianco P, 2001, STEM CELLS, V19, P180, DOI 10.1634/stemcells.19-3-180 Chiocca EA, 2004, MOL THER, V10, P958, DOI 10.1016/j.ymthe.2004.07.021 Conget PA, 2000, EXP HEMATOL, V28, P382, DOI 10.1016/S0301-472X(00)00134-X Ehtesham M, 2004, NEOPLASIA, V6, P287, DOI 10.1593/neo.03427 Ehtesham M, 2002, CANCER RES, V62, P5657 Ehtesham Moneeb, 2005, Neurosurg Focus, V19, pE5 FRIEDENSTEIN AJ, 1987, CELL TISSUE KINET, V20, P263, DOI 10.1111/j.1365-2184.1987.tb01309.x Honczarenko M, 2006, STEM CELLS, V24, P1030, DOI 10.1634/stemcells.2005-0319 Ichikawa T, 2001, CANCER RES, V61, P5336 Knaän-Shanzer S, 2005, STEM CELLS, V23, P1598, DOI 10.1634/stemcells.2005-0016 Komarova S, 2006, MOL CANCER THER, V5, P755, DOI 10.1158/1535-7163.MCT-05-0334 Lang FF, 2003, J CLIN ONCOL, V21, P2508, DOI 10.1200/JCO.2003.21.13.2508 Lee RH, 2004, CELL PHYSIOL BIOCHEM, V14, P311, DOI 10.1159/000080341 Lesniak MS, 2006, EXPERT REV ANTICANC, V6, pS1, DOI 10.1586/14737140.6.9s.S1 Lichtenstein DL, 2004, CANCER GENE THER, V11, P819, DOI 10.1038/sj.cgt.7700765 LOPEZ PA, 2007, STEM CELLS, V25, P1737 Louis DN, 2001, AM J PATHOL, V159, P779, DOI 10.1016/S0002-9440(10)61750-6 Majem M, 2006, CANCER GENE THER, V13, P696, DOI 10.1038/sj.cgt.7700940 Nakamizo A, 2005, CANCER RES, V65, P3307, DOI 10.1158/0008-5472.CAN-04-1874 Nakamura K, 2004, GENE THER, V11, P1155, DOI 10.1038/sj.gt.3302276 Sandmair AM, 2000, HUM GENE THER, V11, P2197, DOI 10.1089/104303400750035726 Serfozo P, 2006, CANCER CELL INT, V6, DOI 10.1186/1475-2867-6-1 Short JJ, 2004, VIROLOGY, V322, P349, DOI 10.1016/j.virol.2004.02.016 Son BR, 2006, STEM CELLS, V24, P1254, DOI 10.1634/stemcells.2005-0271 Sonabend AM, 2006, REV MED VIROL, V16, P99, DOI 10.1002/rmv.490 Sordi V, 2005, BLOOD, V106, P419, DOI 10.1182/blood-2004-09-3507 STOFF K, 2007, BREAST CANC RES TREA, V105, P157 Suzuki K, 2001, CLIN CANCER RES, V7, P120 Tekant Y, 2005, SURGERY, V137, P527, DOI 10.1016/j.surg.2004.12.014 Tyler MA, 2006, MOL CANCER THER, V5, P2408, DOI 10.1158/1535-7163.MCT-06-0187 Ulasov IV, 2007, HUM GENE THER, V18, P589, DOI 10.1089/hum.2007.002 Ulasov IV, 2007, CANCER BIOL THER, V6, P679, DOI 10.4161/cbt.6.5.3957 Ulasov IV, 2006, HUM GENE THER, V17, P556, DOI 10.1089/hum.2006.17.556 van Houdt WJ, 2006, J NEUROSURG, V104, P583, DOI 10.3171/jns.2006.104.4.583 Zheng S, 2007, J GENE MED, V9, P151, DOI 10.1002/jgm.1008 Zhu ZB, 2005, INT J ONCOL, V27, P237 Zhu ZB, 2007, LUNG CANCER, V55, P145, DOI 10.1016/j.lungcan.2006.10.012 Zimmermann B, 2005, CLIN CHEM, V51, P1598, DOI 10.1373/clinchem.2005.051235 Ziu M, 2006, J NEURO-ONCOL, V79, P125, DOI 10.1007/s11060-006-9121-5 NR 41 TC 212 Z9 232 U1 0 U2 17 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 EI 1549-4918 J9 STEM CELLS JI Stem Cells PY 2008 VL 26 IS 3 BP 831 EP 841 DI 10.1634/stemcells.2007-0758 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 278RU UT WOS:000254304800027 PM 18192232 DA 2025-10-02 ER PT J AU Srinivasan, VM Gumin, J Camstra, KM Collins, DE Chen, MM Shpall, EJ Kerrigan, BCP Johnson, JN Chen, SR Fueyo, J Gomez-Manzano, C Lang, FF Kan, P AF Srinivasan, Visish M. Gumin, Joy Camstra, Kevin M. Collins, Dalis E. Chen, Melissa M. Shpall, Elizabeth J. Kerrigan, Brittany C. Parker Johnson, Jeremiah N. Chen, Stephen R. Fueyo, Juan Gomez-Manzano, Cande Lang, Frederick F. Kan, Peter TI Endovascular Selective Intra-Arterial Infusion of Mesenchymal Stem Cells Loaded With Delta-24 in a Canine Model SO NEUROSURGERY LA English DT Article DE Endovascular; Cerebrovascular; Glioma; Glioblastoma; Microcatheter; Superselective; Intra-arterial ID IN-VIVO; TROPISM AB BACKGROUND Delta-24-RGD, an oncolytic adenovirus, shows promise against glioblastoma. To enhance virus delivery, we recently demonstrated that human bone marrow-derived mesenchymal stem cells loaded with Delta-24-RGD (hMSC-D24) can eradicate glioblastomas in mouse models. There are no studies examining the safety of endovascular selective intra-arterial (ESIA) infusions of MSC-D24 in large animals simulating human clinical situations. OBJECTIVE To perform canine preclinical studies testing the feasibility and safety of delivering increasing doses of hMSCs-D24 via ESIA infusions. METHODS ESIA infusions of hMSC-D24 were performed in the cerebral circulation of 10 normal canines in the target vessels (internal carotid artery [ICA]/P1) via transfemoral approach using commercially available microcatheters. Increasing concentrations of hMSC-D24 or particles (as a positive control) were injected into 1 hemisphere; saline (negative control) was infused contralaterally. Toxicity (particularly embolic stroke) was assessed on postinfusion angiography, diffusion-weighted magnetic resonance imaging, clinical exam, and necropsy. RESULTS ESIA injections were performed in the ICA (n = 7) or P1 (n = 3). In 2 animals injected with particles (positive control), strokes were detected by all assays. Of 6 canines injected with hMSC-D24 through the anterior circulation, escalating dose from 2 x 10(6) cells/20 mL to 1 x 10(8) cells/10 mL resulted in no strokes. Two animals had ischemic and hemorrhagic strokes after posterior cerebral artery catheterization. A survival experiment of 2 subjects resulted in no complications detected for 24-h before euthanization. CONCLUSION This novel study simulating ESIA infusion demonstrates that MSCs-D24 can be infused safely at least up to doses of 1 x 10(8) cells/10 mL (10(7) cells/ml) in the canine anterior circulation using commercially available microcatheters. These findings support a clinical trial of ESIA infusion of hMSCs-D24. C1 [Srinivasan, Visish M.; Gumin, Joy; Kerrigan, Brittany C. Parker; Lang, Frederick F.; Kan, Peter] Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. [Camstra, Kevin M.; Johnson, Jeremiah N.; Kan, Peter] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX USA. [Collins, Dalis E.] Baylor Coll Med, Ctr Comparat Med, Houston, TX USA. [Chen, Melissa M.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX USA. [Shpall, Elizabeth J.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Houston, TX USA. [Chen, Stephen R.] Univ Texas MD Anderson Canc Ctr, Dept Intervent Radiol, Houston, TX USA. [Fueyo, Juan; Gomez-Manzano, Cande] Univ Texas MD Anderson Canc Ctr, Dept Neuro Oncol, Houston, TX USA. C3 Baylor College of Medicine; University of Texas System; UTMD Anderson Cancer Center; Baylor College of Medicine; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center; University of Texas System; UTMD Anderson Cancer Center RP Kan, P (corresponding author), Dept Neurosurg, 250 Blossom St 4th Floor, Webster, TX 77598 USA. 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The success of any given gene-therapy is highly dependent on the carrier efficiency. New approaches are often revisiting the mythic trojan horse concept to carry therapeutic nucleic acid, i.e. DNAs, RNAs or small interfering RNAs, to pathologic tumor site. Recent investigations are focusing on engineering carrying modalities to overtake the above limitations bringing new promise to cancer patients. This review describes recent advances and perspectives for gene therapies devoted to tumor treatment, taking advantage of available knowledge in biotechnology and medicine. (C) 2013 Elsevier B.V. All rights reserved. C1 [Collet, Guillaume; Grillon, Catherine; Nadim, Mahdi; Kieda, Claudine] CNRS, Ctr Biophys Mol, UPR4301, F-45071 Orleans 2, France. [Nadim, Mahdi] Libragen Induchem Co, F-31400 Toulouse, France. 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Levesque, Sarah Workenhe, Samuel T. Gujar, Shashi Le Boeuf, Fabrice Clements, Derek R. Fahrner, Jean-Eudes Fend, Laetitia Bell, John C. Mossman, Karen L. Fucikova, Jitka Spisek, Radek Zitvogel, Laurence Kroemer, Guido Galluzzi, Lorenzo TI Trial Watch: Oncolytic viro-immunotherapy of hematologic and solid tumors SO ONCOIMMUNOLOGY LA English DT Review DE CAVATAK; DNX-2401; HF10; Maraba MG1; MV-NIS; Pexa-Vec; REOLYSIN; T-VEC ID HERPES-SIMPLEX-VIRUS; VESICULAR STOMATITIS-VIRUS; NEWCASTLE-DISEASE VIRUS; IMMUNOGENIC CELL-DEATH; IMMUNE CHECKPOINT BLOCKADE; MESENCHYMAL STROMAL CELLS; COLONY-STIMULATING FACTOR; RANDOMIZED PHASE-2 TRIAL; FIBROBLAST-GROWTH-FACTOR; SEMLIKI-FOREST-VIRUS AB Oncolytic viruses selectively target and kill cancer cells in an immunogenic fashion, thus supporting the establishment of therapeutically relevant tumor-specific immune responses. In 2015, the US Food and Drug Administration (FDA) approved the oncolytic herpes simplex virus T-VEC for use in advanced melanoma patients. Since then, a plethora of trials has been initiated to assess the safety and efficacy of multiple oncolytic viruses in patients affected with various malignancies. Here, we summarize recent preclinical and clinical progress in the field of oncolytic virotherapy. C1 [Pol, Jonathan G.; Levesque, Sarah; Fahrner, Jean-Eudes; Zitvogel, Laurence; Kroemer, Guido] Gustave Roussy Comprehens Canc Inst, Villejuif, France. [Pol, Jonathan G.; Levesque, Sarah; Kroemer, Guido] INSERM, Paris, France. [Pol, Jonathan G.; Levesque, Sarah; Kroemer, Guido] Ctr Rech Cordeliers, Equipe Labellisee Ligue Natl Canc 11, Paris, France. [Pol, Jonathan G.; Levesque, Sarah; Kroemer, Guido; Galluzzi, Lorenzo] Univ Paris Descartes Paris V, Sorbonne Paris Cite, Paris, France. [Pol, Jonathan G.; Levesque, Sarah; Kroemer, Guido] Univ Pierre & Marie Curie Paris VI, Paris, France. [Workenhe, Samuel T.; Mossman, Karen L.] McMaster Univ, McMaster Immunol Res Ctr, Hamilton, ON, Canada. [Workenhe, Samuel T.; Mossman, Karen L.] McMaster Univ, Inst Infect Dis Res, Hamilton, ON, Canada. [Workenhe, Samuel T.; Mossman, Karen L.] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Gujar, Shashi; Clements, Derek R.] Dalhousie Univ, Dept Pathol, Halifax, NS, Canada. [Gujar, Shashi] Dalhousie Univ, Dept Microbiol & Immunol, Halifax, NS, Canada. [Gujar, Shashi] Dalhousie Univ, Dept Biol, Halifax, NS, Canada. [Gujar, Shashi] IWK Hlth Ctr, Ctr Innovat & Collaborat Hlth Sci Res Qual & Syst, Halifax, NS, Canada. [Le Boeuf, Fabrice; Bell, John C.] Ottawa Hosp, Res Inst, Canc Therapeut, Ottawa, ON, Canada. [Le Boeuf, Fabrice; Bell, John C.] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada. [Fahrner, Jean-Eudes; Zitvogel, Laurence] INSERM, Villejuif, France. [Fahrner, Jean-Eudes; Fend, Laetitia] Transgene SA, Illkirch Graffenstaden, France. [Fucikova, Jitka; Spisek, Radek] Sotio Ac, Prague, Czech Republic. [Fucikova, Jitka; Spisek, Radek] Charles Univ Prague, Univ Hosp Motol, Fac Med 2, Dept Immunol, Prague, Czech Republic. [Kroemer, Guido] Gustave Roussy Canc Campus, Metabol & Cell Biol Platforms, Villejuif, France. [Kroemer, Guido] Hop Europeen Georges Pompidou, Pole Biol, Paris, France. [Kroemer, Guido] Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Stockholm, Sweden. [Galluzzi, Lorenzo] Weill Cornell Med Coll, Dept Radiat Oncol, New York, NY USA. [Galluzzi, Lorenzo] Sandra & Edward Meyer Canc Ctr, New York, NY USA. C3 Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Sorbonne Universite; Universite Paris Cite; Sorbonne Universite; McMaster University; McMaster University; McMaster University; Dalhousie University; Dalhousie University; Dalhousie University; Dalhousie University; Dalhousie University Hospital; University of Ottawa; Ottawa Hospital Research Institute; University of Ottawa; Institut National de la Sante et de la Recherche Medicale (Inserm); Transgene SA; Motol University Hospital; Charles University Prague; UNICANCER; Gustave Roussy; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Europeen Georges-Pompidou - APHP; Karolinska Institutet; Karolinska University Hospital; Cornell University; Weill Cornell Medicine RP Pol, JG; Kroemer, G (corresponding author), Ctr Rech Cordeliers, INSERM, U1138, 15 Rue Ecole Med, F-75006 Paris, France.; Galluzzi, L (corresponding author), Weill Cornell Med Coll, Dept Radiat Oncol, 525 East 68th St,Box 169, New York, NY 10065 USA. EM pol_jonathan@yahoo.fr; kroemer@orange.fr; deadoc@vodafone.it RI Fahrner, Jean-Eudes/AAK-9264-2021; Pol, Jonathan/R-6507-2016; Galluzzi, Lorenzo/AAG-6432-2019; KROEMER, Guido/B-4263-2013 OI Fahrner, Jean-Eudes/0000-0001-6581-8418; ZITVOGEL, laurence/0000-0003-1596-0998; Gujar, Shashi/0000-0002-5427-0829; Pol, Jonathan/0000-0002-8355-7562 FU Department of Radiation Oncology of Weill Cornell Medical College (New York, US); Ligue contre le Cancer (Equipe labelisee); Agence Nationale de la Recherche (ANR)-Projets blancs; ANR; ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer (ARC); Canceropole Ile-de-France; Institut National du Cancer (INCa); Institut Universitaire de France; Fondation pour la Recherche Medicale [FDM20140630126, FDM 40739]; European Commission (ArtForce); European Research Council (ERC); Leducq Foundation; Seerave Foundation; LabEx Immuno-Oncology; RHU Torino Lumiere; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); SIRIC Cancer Research and Personalized Medicine (CARPEM); Paris Alliance of Cancer Research Institutes (PACRI) FX LG is supported by an intramural startup from the Department of Radiation Oncology of Weill Cornell Medical College (New York, US), and by donations from Sotio a.s. (Prague, Czech Republic) and Phosplatin (New York, US). GK is supported by the Ligue contre le Cancer (Equipe labelisee); Agence Nationale de la Recherche (ANR)-Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer (ARC); Canceropole Ile-de-France; Institut National du Cancer (INCa); Institut Universitaire de France; Fondation pour la Recherche Medicale (FDM20140630126 and FDM 40739); the European Commission (ArtForce); the European Research Council (ERC); the Leducq Foundation; the Seerave Foundation; the LabEx Immuno-Oncology; the RHU Torino Lumiere; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); and the Paris Alliance of Cancer Research Institutes (PACRI). 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7 IS 12 AR e1503032 DI 10.1080/2162402X.2018.1503032 PG 32 WC Oncology; Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Immunology GA HA7LE UT WOS:000450462000017 PM 30524901 OA Green Submitted, gold DA 2025-10-02 ER PT J AU Morales-Molina, A Gambera, S Leo, A García-Castro, J AF Morales-Molina, Alvaro Gambera, Stefano Leo, Angela Garcia-Castro, Javier TI Combination immunotherapy using G-CSF and oncolytic virotherapy reduces tumor growth in osteosarcoma SO JOURNAL FOR IMMUNOTHERAPY OF CANCER LA English DT Article DE immunotherapy; lymphocytes; tumor-infiltrating; oncolytic virotherapy; programmed cell death 1 receptor; t-lymphocytes ID MESENCHYMAL STEM-CELLS; 1ST-IN-CHILD TRIAL; VIRUS ICOVIR-5; CARRIER CELLS; ADENOVIRUS; PROTEIN; POTENT; PRB; NEUROBLASTOMA; CHEMOTHERAPY AB Background Osteosarcoma is the most common malignant solid tumor that affects bones, however, survival rates of patients with relapsed osteosarcoma have not improved in the last 30 years. Oncolytic virotherapy, which uses viruses designed to selectively replicate in cancer cells, has emerged as a promising treatment for solid tumors. Our group uses mesenchymal stem cells (MSCs) to transport oncolytic adenoviruses (OAds) to the tumor site, a therapeutic strategy called Celyvir. This treatment has been already applied in human patients, canine patients and different mouse models. In parallel, previous results have probed that administration of granulocyte-colony stimulating factor (G-CSF) increased immune infiltration in tumors. We then hypothesized that the mobilization of immune cells by G-CSF may increase the antitumor efficacy of Celyvir treatment by increasing the immune infiltration into the tumors. Methods In this study, we use a murine version of Celyvir consisting in murine MSCs carrying the murine OAd dlE102-here called OAd-MSCs-in an immunocompetent model of osteosarcoma. We tested the antitumoral efficacy of the combination of OAd-MSCs plus G-CSF. Results Our results show that treatment with OAd-MSCs or the union of OAd-MSCs with G-CSF (Combination) significantly reduced tumor growth of osteosarcoma in vivo. Moreover, treated tumors presented higher tumor infiltration of immune cells-especially tumor-infiltrating lymphocytes-and reduced T cell exhaustion, which seems to be enhanced in tumors treated with the Combination. The comparison of our results to those obtained from a cohort of pediatric osteosarcoma patients showed that the virotherapy induces immunological changes similar to those observed in patients with good prognosis. Conclusions The results open the possibility of using cellular virotherapy for the treatment of bone cancers. Indeed, its combination with G-CSF may be considered for the improvement of the therapy. C1 [Morales-Molina, Alvaro; Gambera, Stefano; Garcia-Castro, Javier] Inst Salud Carlos III, Cellular Biotechnol Unit, Madrid, Spain. [Leo, Angela] Univ Florence, Dept Biomed Expt & Clin Sci, Florence, Italy. C3 Instituto de Salud Carlos III; University of Florence RP García-Castro, J (corresponding author), Inst Salud Carlos III, Cellular Biotechnol Unit, Madrid, Spain. EM jgcastro@isciii.es RI Gambera, Stefano/X-8631-2019; Garcia-Castro, Javier/ABC-9741-2021; Garcia-Castro, Javier/H-5274-2011 OI Leo, Angela/0000-0002-7564-9627; Morales-Molina, Alvaro/0000-0003-4532-7667; Garcia-Castro, Javier/0000-0001-7604-1640 FU Instituto de Salud Carlos III of Spain [PI14CIII/00005, PI17CIII/00013]; Consejeria de Educacion, Juventud y Deporte of Comunidad de Madrid [P2017/BMD-3692]; Fundacion Oncohematologia Infantil; Asociacion Pablo Ugarte; AFANION FX This study was funded by the Instituto de Salud Carlos III of Spain (grant numbers PI14CIII/00005 and PI17CIII/00013), Consejeria de Educacion, Juventud y Deporte of Comunidad de Madrid (grant number P2017/BMD-3692), Fundacion Oncohematologia Infantil, Asociacion Pablo Ugarte and AFANION, whose support we gratefully acknowledge. 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Immunother. Cancer PY 2021 VL 9 IS 3 AR e001703 DI 10.1136/jitc-2020-001703 PG 13 WC Oncology; Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Immunology GA RA6KJ UT WOS:000631525400001 PM 33737338 OA Green Published, gold DA 2025-10-02 ER PT J AU Seyed-Khorrami, SM Soleimanjahi, H Soudi, S Habibian, A AF Seyed-Khorrami, Seyed-Mahmood Soleimanjahi, Hoorieh Soudi, Sara Habibian, Ala TI MSCs loaded with oncolytic reovirus: migration and in vivo virus delivery potential for evaluating anti-cancer effect in tumor-bearing C57BL/6 mice SO CANCER CELL INTERNATIONAL LA English DT Article DE Drug Delivery Systems; Targeted therapy; IFN-γ Anti-tumor effect; MOI; Virus titer ID MESENCHYMAL STEM-CELLS; STROMAL CELLS; OVARIAN-CANCER; GENE-THERAPY; ANTITUMOR-ACTIVITY; EXOSOMES; REPLICATION; ADENOVIRUS; APOPTOSIS; ENHANCE AB Background and aims Several oncolytic viruses applications have been approved in the clinic or in different phases of clinical trials. However, these methods have some rudimentary problems. Therefore, to enhance the delivery and quality of treatment, considering the advantage of cell carrier-based methods such as Mesenchymal Stem Cells (MSC) have been proposed. This study was designed to evaluate the performance and quality of cancer treatment based on MSCs loaded by oncolytic reovirus in the cancerous C57BL/6 mouse model. Also, we evaluated MSCs migration potency in vitro and in vivo following the oncolytic reovirus infection. Methods C57BL/6 mice were inoculated with TC-1 cell lines and tumors were established in the right flank. Mice were systemically treated with reovirus, MSCs-loaded with reovirus, MSCs, and PBS as a control in separated groups. Effects of infected AD-MSCs with reovirus on tumor growth and penetration in the tumor site were monitored. All groups of mice were monitored for two months in order to therapeutic and anticancer potential. After treatments, tumor size alteration and apoptosis rate, as well as cytokine release pattern was assessed. Results The results of the current study indicated that the effect of reovirus infection on AD-MSCs is not devastating the migration capacity especially in MOI 1 and 5 while intact cells remain. On the other hand, MSCs play an efficient role as a carrier to deliver oncolytic virus into the tumor site in comparison with systemic administration of reovirus alone. Apoptosis intensity relies on viral titration and passing time. Followed by systemic administration, treatment with oncolytic reovirus-infected AD-MSCs and MSCs alone had shown significant inhibition in tumor growth. Also, treatment by reovirus causes an increase in IFN-gamma secretion. Conclusion The results of in vitro and in vivo study confirmed the tumor-homing properties of infected AD-MSCs and the significant antitumor activity of this platform. Hence, our results showed that the cell carrier strategy using oncolytic reovirus-loaded AD-MSCs enhanced virus delivery, infiltration, and antitumor activity can be effectively applied in most cancers. C1 [Seyed-Khorrami, Seyed-Mahmood; Soleimanjahi, Hoorieh; Habibian, Ala] Tarbiat Modares Univ, Fac Med Sci, Dept Virol, Tehran, Iran. [Soudi, Sara] Tarbiat Modares Univ, Fac Med Sci, Dept Immunol, Tehran, Iran. C3 Tarbiat Modares University; Tarbiat Modares University RP Soleimanjahi, H (corresponding author), Tarbiat Modares Univ, Fac Med Sci, Dept Virol, Tehran, Iran. EM soleim_h@modares.ac.ir RI Soleimanjahi, Hoorieh/Y-7846-2019; Soleimanjahi, Hoorieh/B-8945-2017 OI Soleimanjahi, Hoorieh/0000-0003-1931-7801; Seyed Khorami, Seyed Mahmood/0000-0002-5043-8292; Habibian, Ala/0000-0003-1817-3834 FU Tarbiat Modares University, Faculty of Medical Sciences [Med-71214]; NIMAD (National Institute for Medical Research Development) [957970] FX This study was performed as part of Ph.D. thesis and financially supported by the deputy of Tarbiat Modares University (Med-71214), Faculty of Medical Sciences, and partially supported by NIMAD (957970) (National Institute for Medical Research Development). 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PD MAY 1 PY 2021 VL 21 IS 1 AR 244 DI 10.1186/s12935-021-01848-5 PG 19 WC Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology GA RW5XT UT WOS:000646597000001 PM 33933086 OA gold, Green Submitted DA 2025-10-02 ER PT J AU Gonzalez-Pastor, R Hernandez, Y Gimeno, M de Martino, A Man, YKS Hallden, G Quintanilla, M de la Fuente, JM Martin-Duque, P AF Gonzalez-Pastor, Rebeca Hernandez, Yulan Gimeno, Marina de Martino, Alba Man, Y. K. Stella Hallden, Gunnel Quintanilla, Miguel de la Fuente, Jesus M. Martin-Duque, Pilar TI Coating an adenovirus with functionalized gold nanoparticles favors uptake, intracellular trafficking and anti-cancer therapeutic efficacy SO ACTA BIOMATERIALIA LA English DT Article DE Adenovirus; Gold nanoparticles; Mesenchymal stem cells; Cancer gene therapy; hNIS ID IN-VIVO; ONCOLYTIC ADENOVIRUS; GENE DELIVERY; NEUTRALIZING ANTIBODIES; SODIUM/IODIDE SYMPORTER; TARGETED DELIVERY; CELLULAR UPTAKE; CANCER-CELLS; RECEPTOR; VECTORS AB Adenoviral (Ad) vectors have proven to be important tools for gene and cell therapy, although some issues still need to be addressed, such as undesired interactions with blood components and off-target seques-tration that ultimately hamper efficacy. In the past years, several organic and inorganic materials have been developed to reduce immunogenicity and improve biodistribution of Ad vectors. Here we investi-gated the influence of the functionalization of 14 nm PEGylated gold nanoparticles (AuNPs) with quater-nary ammonium groups and an arginine-glycine-aspartic acid (RGD)-motif on the uptake and biodistri-bution of Ad vectors. We report the formation of Ad@AuNPs complexes that promote cell attachment and uptake, independently of the presence of the coxsackievirus and adenovirus receptor (CAR) and alpha(v)beta(3) and alpha(v)beta(5) integrins, significantly improving transduction without limiting Ad bioactivity. Besides, the presence of the RGD peptide favors tumor targeting and decreases Ad sequestration in the liver. Additionally, tumor delivery of a coated Ad vector expressing the human sodium iodide symporter (hNIS) by mesenchymal stem cells induces increased accumulation of radioactive iodine (I-131) and tumor volume reduction com-pared to naked Ad-hNIS, highlighting the promising potential of our coating formulation in cancer gene therapy. Statement of significance Modification of adenoviral vectors with lipids and polymers can reduce interactions with blood compo-nents and increase tumor accumulation; however, increased toxicity and reduced transduction efficiency were indicated. Coating with gold nanoparticles has proven to be a successful strategy for increasing the efficiency of transduction of receptor-defective cell lines. Here we explore the contribution of cell sur -face receptors on the mechanisms of entry of Ad vectors coated with gold nanoparticles in cell lines with varying degrees of resistance to infection. The enhancement of the anti-tumoral effect shown in this work provides new evidence for the potential of our formulation. (c) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Gonzalez-Pastor, Rebeca; de Martino, Alba; Martin-Duque, Pilar] Inst Aragones Ciencias Salud IACS IIS Aragon, Ctr Invest Biomed Aragon CIBA, Avda San Juan Bosco 13,Planta 0, Zaragoza 50009, Spain. [Hernandez, Yulan] Pontificia Univ Catolica Peru PUCP, Dept Ciencias, Secc Quim, Lima, Peru. [Gimeno, Marina] Univ Zaragoza, Fac Vet, Zaragoza 50013, Spain. [Man, Y. K. Stella; Hallden, Gunnel] Queen Mary Univ London, Barts Canc Inst, London, England. [Quintanilla, Miguel] Inst Invest Biomed Alberto Sols CSIC, Madrid 28029, Spain. [de la Fuente, Jesus M.] Univ Zaragoza, Inst Nanociencia & Mat Aragon INMA, CSIC, Zaragoza 50018, Spain. [de la Fuente, Jesus M.; Martin-Duque, Pilar] Ctr Invest Biomed Red Bioingn Biomat & Nanomed CI, Madrid 28029, Spain. [Martin-Duque, Pilar] Fdn Araid, Zaragoza 50001, Spain. C3 Pontificia Universidad Catolica del Peru; University of Zaragoza; University of London; Queen Mary University London; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC - Instituto de Investigaciones Biomedicas Alberto Sols (IIBM); Consejo Superior de Investigaciones Cientificas (CSIC); University of Zaragoza; CIBER - Centro de Investigacion Biomedica en Red; CIBERBBN RP Martin-Duque, P (corresponding author), Inst Aragones Ciencias Salud IACS IIS Aragon, Ctr Invest Biomed Aragon CIBA, Avda San Juan Bosco 13,Planta 0, Zaragoza 50009, Spain. 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PD OCT 15 PY 2021 VL 134 BP 593 EP 604 DI 10.1016/j.actbio.2021.07.047 EA OCT 2021 PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials WE Science Citation Index Expanded (SCI-EXPANDED) SC Engineering; Materials Science GA WK8IC UT WOS:000709963900005 PM 34325075 DA 2025-10-02 ER PT J AU Abd-Aziz, N Poh, CL AF Abd-Aziz, Noraini Poh, Chit Laa TI Development of oncolytic viruses for cancer therapy SO TRANSLATIONAL RESEARCH LA English DT Review DE Oncolytic virus; Cancer; Combination therapy; Clinical trials ID NEWCASTLE-DISEASE VIRUS; MESENCHYMAL STEM-CELLS; PHASE-I TRIAL; IMMUNOTHERAPEUTIC VACCINIA VIRUS; RECURRENT MALIGNANT GLIOMAS; VESICULAR STOMATITIS-VIRUS; SODIUM-IODIDE SYMPORTER; PEXA-VEC JX-594; MEASLES-VIRUS; TALIMOGENE LAHERPAREPVEC AB Oncolytic virotherapy is a therapeutic approach that uses replication-competent viruses to kill cancers. The ability of oncolytic viruses to selectively replicate in cancer cells leads to direct cell lysis and induction of anticancer immune response. Like other anticancer therapies, oncolytic virotherapy has several limitations such as viral delivery to the target, penetration into the tumor mass, and antiviral immune responses. This review provides an insight into the different characteristics of oncolytic viruses (natural and genetically modified) that contribute to effective applications of oncolytic virotherapy in preclinical and clinical trials, and strategies to overcome the limitations. The potential of oncolytic virotherapy combining with other conventional treatments or cancer immunotherapies involving immune checkpoint inhibitors and CAR-T therapy could form part of future multimodality treatment strategies. (Translational Research 2021; 237:98-123) C1 [Abd-Aziz, Noraini; Poh, Chit Laa] Sunway Univ, Ctr Virus & Vaccine Res CVVR, Sch Med & Life Sci, Subang Jaya 47500, Selangor, Malaysia. C3 Sunway University RP Poh, CL (corresponding author), Sunway Univ, Ctr Virus & Vaccine Res CVVR, Sch Med & Life Sci, Subang Jaya 47500, Selangor, Malaysia. EM pohcl@sunway.edu.my RI Abd-Aziz, Noraini/GLQ-9183-2022; LAA, POH/B-9498-2010 FU Sunway University [STR-RCTR-CVVR-01-2020] FX The authors of this review gratefully acknowledge the research support from Sunway University. This work was funded by the Sunway University Research Centre Scheme STR-RCTR-CVVR-01-2020 to the Centre for Virus and Vaccine Research (CVVR) . 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Res. PD NOV PY 2021 VL 237 BP 98 EP 123 DI 10.1016/j.trsl.2021.04.008 EA SEP 2021 PG 26 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA YV1TQ UT WOS:000752515800007 PM 33905949 DA 2025-10-02 ER PT J AU Hammad, M Cornejo, YR Batalla-Covello, J Majid, AA Burke, C Liu, Z Yuan, YC Li, M Dellinger, TH Lu, JM Chen, NG Fong, YM Aboody, KS Mooney, R AF Hammad, Mohamed Cornejo, Yvonne R. Batalla-Covello, Jennifer Majid, Asma Abdul Burke, Connor Liu, Zheng Yuan, Yate-Ching Li, Min Dellinger, Thanh H. Lu, Jianming Chen, Nanhai G. Fong, Yuman Aboody, Karen S. Mooney, Rachael TI Neural Stem Cells Improve the Delivery of Oncolytic Chimeric Orthopoxvirus in a Metastatic Ovarian Cancer Model SO MOLECULAR THERAPY-ONCOLYTICS LA English DT Article ID MEASLES VIROTHERAPY; VIRUS; CARRIERS; THERAPY; ADENOVIRUS; NEUTRALIZATION; GLIOMA; BRAIN AB Oncolytic virotherapy represents a promising approach for treating recurrent and/or drug-resistant ovarian cancer. However, its successful application in the clinic has been hampered by rapid immune-mediated clearance, which reduces viral delivery to the tumor. Patient-derived mesenchymal stem cells that home to tumors have been used as viral delivery tools, but variability associated with autologous cell isolations limits the clinical applicability of this approach. We previously developed an allogeneic, clonal neural stem cell (NSC) line (HB1.F3.CD21) that can be used to deliver viral cargo. Here, we demonstrate that this NSC line can improve the delivery of a thymidine kinase gene-deficient conditionally replication-competent orthopoxvirus, CF33, in a preclinical cisplatin-resistant peritoneal ovarian metastases model. Overall, our findings provide the basis for using off-the-shelf allogeneic cell-based delivery platforms for oncolytic viruses, thus providing a more efficient delivery alternative compared with the free virus administration approach. C1 [Hammad, Mohamed; Cornejo, Yvonne R.; Batalla-Covello, Jennifer; Majid, Asma Abdul; Burke, Connor; Aboody, Karen S.; Mooney, Rachael] City Hope Natl Med Ctr, Dept Dev & Stem Cell Biol, Duarte, CA 91010 USA. [Cornejo, Yvonne R.; Batalla-Covello, Jennifer] Irell & Manella Grad Sch Biol Sci, City Hope, Beckman Res Ins, Duarte, CA 91010 USA. [Liu, Zheng; Yuan, Yate-Ching] City Hope Natl Med Ctr, Translat Bioinformat Div, Ctr Informat, Duarte, CA 91010 USA. [Li, Min] City Hope Natl Med Ctr, Dept Informat Sci, Div Biostat, Beckman Res Inst, Duarte, CA 91010 USA. [Dellinger, Thanh H.] City Hope Natl Med Ctr, Div Gynecol Surg, Dept Surg, Duarte, CA 91010 USA. [Lu, Jianming; Chen, Nanhai G.; Fong, Yuman] City Hope Natl Med Ctr, Dept Surg, Duarte, CA 91010 USA. [Chen, Nanhai G.; Fong, Yuman] City Hope Natl Med Ctr, Ctr Gene Therapy, Duarte, CA 91010 USA. [Aboody, Karen S.] City Hope Natl Med Ctr, Div Neurosurg, Duarte, CA 91010 USA. C3 City of Hope; City of Hope; City of Hope; City of Hope; Beckman Research Institute of City of Hope; City of Hope; City of Hope; City of Hope; City of Hope RP Hammad, M; Mooney, R (corresponding author), City Hope Natl Med Ctr, Dept Dev & Stem Cell Biol, 1500 East Duarte Ave, Duarte, CA 91010 USA. EM mhammad@coh.org; rmooney@coh.org RI Chen, George/MXK-5233-2025; Burke, Connor/HHD-1284-2022; lu, jm/JPK-3675-2023 OI Covello, Jennifer/0000-0002-7206-8421 FU Stop Cancer; Rosalinde and Arthur Gilbert Foundation; California Institute of Regenerative Medicine; Alvarez Family Foundation; Anthony F. & Susan M. Markel Foundation; Ben and Catherine Ivy Foundation, City of Hope; National Cancer Institute [R43CA86768, R44CA8678, R01CA197359]; National Cancer Institute of the NIH [P30CA033572] FX This work was funded by Stop Cancer, The Rosalinde and Arthur Gilbert Foundation, California Institute of Regenerative Medicine, the Alvarez Family Foundation, the Anthony F. & Susan M. Markel Foundation, the Ben and Catherine Ivy Foundation, City of Hope, and National Cancer Institute grants (R43CA86768, R44CA8678, and R01CA197359). Research reported in this publication included work performed by X.L. in the City of Hope Biostatistics Core, which is supported by the National Cancer Institute of the NIH under award number P30CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Materials Transfer Information is available from the City of Hope Office of Technology Licensing. Special thanks for COH scientific writers Kerin Higa, PhD, and Supriya Deshpande, PhD, for editing this manuscript. 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Ther.-Oncolytics PD SEP 25 PY 2020 VL 18 BP 326 EP 334 DI 10.1016/j.omto.2020.07.002 PG 9 WC Oncology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Research & Experimental Medicine GA NW7AL UT WOS:000575168700053 PM 32775617 OA Green Published, gold DA 2025-10-02 ER PT J AU Sousa, MFQ Silva, MM Roldao, A Alves, PM Serra, M Giroux, D Hashimura, Y Wesselschmidt, R Lee, B Carrondo, MJT AF Sousa, Marcos F. Q. Silva, Marta M. Roldao, Antonio Alves, Paula M. Serra, Margarida Giroux, Daniel Hashimura, Yas Wesselschmidt, Robin Lee, Brian Carrondo, Manuel J. T. TI Production of Oncolytic Adenovirus and Human Mesenchymal Stem Cells in a Single-Use, Vertical-Wheel Bioreactor System: Impact of Bioreactor Design on Performance of Microcarrier-Based Cell Culture Processes SO BIOTECHNOLOGY PROGRESS LA English DT Article DE anchorage-dependent cell cultures; scalability; microcarriers; single-use bioreactor; vertical-wheel bioreactor; hMSC; Onco-Ad5 ID STROMAL CELLS; TURBULENT-FLOW; CHO-CELLS; EXPANSION; DIFFERENTIATION; GROWTH; OPTIMIZATION; MODULATION; VECTORS; DAMAGE AB Anchorage-dependent cell cultures are used for the production of viruses, viral vectors, and vaccines, as well as for various cell therapies and tissue engineering applications. Most of these applications currently rely on planar technologies for the generation of biological products. However, as new cell therapy product candidates move from clinical trials towards potential commercialization, planar platforms have proven to be inadequate to meet large-scale manufacturing demand. Therefore, a new scalable platform for culturing anchorage-dependent cells at high cell volumetric concentrations is urgently needed. One promising solution is to grow cells on microcarriers suspended in single-use bioreactors. Toward this goal, a novel bioreactor system utilizing an innovative Vertical-Wheel technology was evaluated for its potential to support scalable cell culture process development. Two anchorage-dependent human cell types were used: human lung carcinoma cells (A549 cell line) and human bone marrow-derived mesenchymal stem cells (hMSC). Key hydrodynamic parameters such as power input, mixing time, Kolmogorov length scale, and shear stress were estimated. The performance of Vertical-Wheel bioreactors (PBS-VW) was then evaluated for A549 cell growth and oncolytic adenovirus type 5 production as well as for hMSC expansion. Regarding the first cell model, higher cell growth and number of infectious viruses per cell were achieved when compared with stirred tank (ST) bioreactors. For the hMSC model, although higher percentages of proliferative cells could be reached in the PBS-VW compared with ST bioreactors, no significant differences in the cell volumetric concentration and expansion factor were observed. Noteworthy, the hMSC population generated in the PBS-VW showed a significantly lower percentage of apoptotic cells as well as reduced levels of HLA-DR positive cells. Overall, these results showed that process transfer from ST bioreactor to PBS-VW, and scale-up was successfully carried out for two different microcarrier-based cell cultures. Ultimately, the data herein generated demonstrate the potential of Vertical-Wheel bioreactors as a new scalable biomanufacturing platform for microcarrier-based cell cultures of complex biopharmaceuticals. (C) 2015 American Institute of Chemical Engineers C1 [Sousa, Marcos F. Q.; Silva, Marta M.; Roldao, Antonio; Alves, Paula M.; Serra, Margarida] Univ Nova Lisboa, Inst Tecnol Quim & Biol Antonio Xavier, P-2780157 Oeiras, Portugal. [Sousa, Marcos F. Q.; Silva, Marta M.; Roldao, Antonio; Alves, Paula M.; Serra, Margarida; Carrondo, Manuel J. T.] iBET, P-2780901 Oeiras, Portugal. [Giroux, Daniel; Hashimura, Yas; Wesselschmidt, Robin; Lee, Brian] PBS Biotech, Irvine, CA USA. [Carrondo, Manuel J. T.] Univ Nova Lisboa, Dept Quim, Fac Ciencias & Tecnol, P-2829516 Monte De Caparica, Portugal. C3 Universidade Nova de Lisboa; Universidade Nova de Lisboa RP Serra, M (corresponding author), Univ Nova Lisboa, Inst Tecnol Quim & Biol Antonio Xavier, Av Republ, P-2780157 Oeiras, Portugal. 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PD NOV-DEC PY 2015 VL 31 IS 6 BP 1600 EP 1612 DI 10.1002/btpr.2158 PG 13 WC Biotechnology & Applied Microbiology; Food Science & Technology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biotechnology & Applied Microbiology; Food Science & Technology GA DA9OZ UT WOS:000368140300018 PM 26289142 DA 2025-10-02 ER PT J AU Franco-Luzón, L García-Mulero, S Sanz-Pamplona, R Melen, G Ruano, D Lassaletta, A Madero, L González-Murillo, A Ramírez, M AF Franco-Luzon, Lidia Garcia-Mulero, Sandra Sanz-Pamplona, Rebeca Melen, Gustavo Ruano, David Lassaletta, Alvaro Madero, Luis Gonzalez-Murillo, Africa Ramirez, Manuel TI Genetic and Immune Changes Associated with Disease Progression under the Pressure of Oncolytic Therapy in A Neuroblastoma Outlier Patient SO CANCERS LA English DT Article DE neuroblastoma; oncolytic virotherapy; T lymphocytes (TILs); bioinformatic analysis; immune landscape ID CELL-RECEPTOR REPERTOIRE; NEURAL-NETWORKS; B-LYMPHOCYTES; CANCER; IMMUNOTHERAPY; VIROTHERAPY; ACTIVATION; EXPRESSION; ICOVIR-5; CHEMOTHERAPY AB Little is known about the effect of oncolytic adenovirotherapy on pediatric tumors. Here we present the clinical case of a refractory neuroblastoma that responded positively to Celyvir (ICOVIR-5 oncolytic adenovirus delivered by autologous mesenchymal stem cells) for several months. We analyzed samples during tumor evolution in order to identify molecular and mutational features that could explain the interactions between treatment and tumor and how the balance between both of them evolved. We identified a higher adaptive immune infiltration during stabilized disease compared to progression, and also a higher mutational rate and T-cell receptor (TCR) diversity during disease progression. Our results indicate an initial active role of the immune system controlling tumor growth during Celyvir therapy. The tumor eventually escaped from the control exerted by virotherapy through acquisition of resistance by the tumor microenvironment that exhausted the initial T cell response. C1 [Franco-Luzon, Lidia; Madero, Luis] Children Oncohematol Fdn, Madrid 28079, Spain. [Garcia-Mulero, Sandra] Univ Barcelona, Fac Med & Hlth Sci, Dept Clin Sci, Barcelona 08036, Spain. [Garcia-Mulero, Sandra; Sanz-Pamplona, Rebeca] Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol ICO, Unit Biomarkers & Susceptibil, ODAP,Oncobell Program, Barcelona 08908, Spain. [Garcia-Mulero, Sandra; Sanz-Pamplona, Rebeca] CIBERESP, Barcelona 08908, Spain. [Melen, Gustavo; Gonzalez-Murillo, Africa; Ramirez, Manuel] Nino Jesus Children Hosp, Biomed Res Fdn, Madrid 28009, Spain. [Melen, Gustavo; Ruano, David; Lassaletta, Alvaro; Madero, Luis; Gonzalez-Murillo, Africa; Ramirez, Manuel] La Princesa Inst Hlth Res, Madrid 28006, Spain. [Madero, Luis] Hosp Infantil Univ Nino Jesus, Oncohematol Unit, Madrid 28009, Spain. C3 University of Barcelona; Institut Catala d'Oncologia; Institut d'Investigacio Biomedica de Bellvitge (IDIBELL); CIBER - Centro de Investigacion Biomedica en Red; CIBERESP RP Ramírez, M (corresponding author), Nino Jesus Children Hosp, Biomed Res Fdn, Madrid 28009, Spain.; Ramírez, M (corresponding author), La Princesa Inst Hlth Res, Madrid 28006, Spain. EM lfluzon@gmail.com; s.garciam@idibell.cat; rebecasanz@iconcologia.net; gustavo.melen@salud.madrid.org; druano64@hotmail.com; lassaalvaro@yahoo.com; luis.madero@salud.madrid.org; africa.gonzalez@salud.madrid.org; manuel.ramirez@salud.madrid.org RI Garcia, Sandra/HLH-8071-2023; Lassaletta, Alvaro/KPY-5557-2024; Ramirez, Manuel/H-7710-2015; Gonzalez, Africa/M-3426-2014; Franco-Luzón, Lidia/AAO-9792-2020; Melen, Gustavo/L-5918-2014; Ruano-Gallego, David/ABB-4157-2021 OI Ramirez, Manuel/0000-0003-0332-6973; Franco Luzon, Lidia/0000-0002-7343-8201; Melen, Gustavo/0000-0001-9743-8903; Garcia-Mulero, Sandra/0000-0003-4931-1267; Sanz-Pamplona, Rebeca/0000-0002-2187-3527; LASSALETTA, ALVARO/0000-0003-2881-1473 FU Instituto de Salud Carlos III [PI13/02487, PI16/02008]; Asociacion Pablo Ugarte; Asociacion NEN; Fundacion Neuroblastoma FX This research was funded by Instituto de Salud Carlos III, grant number PI13/02487 and PI16/02008. The APC was funded by Asociacion Pablo Ugarte, YAsociacion NEN and Fundacion Neuroblastoma. 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Boulaiz, Houria TI Recent Progress in Gene Therapy for Ovarian Cancer SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Review DE ovarian cancer; gene therapy; delivery systems; promoter; suicide genes; ovarian cancer stem cells ID SHORT HAIRPIN RNA; I CLINICAL-TRIAL; CONDITIONALLY-REPLICATIVE ADENOVIRUS; PEI-CHOLESTEROL LIPOPOLYMER; OVERCOME DRUG-RESISTANCE; VIRUS-MEDIATED DELIVERY; MESENCHYMAL STEM-CELLS; PHASE-I; EFFICIENT INHIBITION; ANTITUMOR-ACTIVITY AB Ovarian cancer is the most lethal gynecological malignancy in developed countries. This is due to the lack of specific symptoms that hinder early diagnosis and to the high relapse rate after treatment with radical surgery and chemotherapy. Hence, novel therapeutic modalities to improve clinical outcomes in ovarian malignancy are needed. Progress in gene therapy has allowed the development of several strategies against ovarian cancer. Most are focused on the design of improved vectors to enhance gene delivery on the one hand, and, on the other hand, on the development of new therapeutic tools based on the restoration or destruction of a deregulated gene, the use of suicide genes, genetic immunopotentiation, the inhibition of tumour angiogenesis, the alteration of pharmacological resistance, and oncolytic virotherapy. In the present manuscript, we review the recent advances made in gene therapy for ovarian cancer, highlighting the latest clinical trials experience, the current challenges and future perspectives. C1 [Ayen, Angela; Marchal, Juan A.; Boulaiz, Houria] Univ Granada, Dept Human Anat & Embryol, Granada 18016, Spain. [Jimenez Martinez, Yaiza; Marchal, Juan A.; Boulaiz, Houria] Univ Granada, Biopathol & Med Regenerat Inst IBIMER, Granada 18016, Spain. [Jimenez Martinez, Yaiza; Marchal, Juan A.; Boulaiz, Houria] Univ Granada, SAS, Biosanitary Inst Granada Ibs GRANADA, Granada 18016, Spain. [Marchal, Juan A.; Boulaiz, Houria] Univ Granada, Excellence Res Unit Modeling Nat MNat, Granada 18016, Spain. C3 University of Granada; University of Granada; Instituto de Investigacion Biosanitaria IBS Granada; University of Granada; University of Granada RP Boulaiz, H (corresponding author), Univ Granada, Dept Human Anat & Embryol, Granada 18016, Spain.; Boulaiz, H (corresponding author), Univ Granada, Biopathol & Med Regenerat Inst IBIMER, Granada 18016, Spain.; Boulaiz, H (corresponding author), Univ Granada, SAS, Biosanitary Inst Granada Ibs GRANADA, Granada 18016, Spain.; Boulaiz, H (corresponding author), Univ Granada, Excellence Res Unit Modeling Nat MNat, Granada 18016, Spain. EM aayen@correo.ugr.es; yaijmartinez@correo.ugr.es; jmarchal@ugr.es; hboulaiz@ugr.es RI Rodríguez, Ángela/AAA-9494-2022; BOULAIZ, HOURIA/H-4253-2015; Marchal, Juan/M-4305-2014; Boulaiz Tassi, Houria/H-4253-2015; Jimenez Martinez, Yaiza/LKN-7130-2024; Marchal, Juan Antonio/M-4305-2014 OI Jimenez Martinez, Yaiza/0000-0003-2936-5831; Boulaiz Tassi, Houria/0000-0003-4433-7556; Marchal, Juan Antonio/0000-0002-4996-8261 FU Fundacion Mutua Madrilena [FMM-AP16683-2017]; Consejeria de Salud Junta de Andalucia [PI-0089-2017]; Chair "Doctors Galera-Requena in cancer stem cell research" FX This research was supported by the Fundacion Mutua Madrilena by the proyect FMM-AP16683-2017, Consejeria de Salud Junta de Andalucia (PI-0089-2017) and from the Chair "Doctors Galera-Requena in cancer stem cell research". 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J. Mol. Sci. PD JUL PY 2018 VL 19 IS 7 AR 1930 DI 10.3390/ijms19071930 PG 29 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA GR6UX UT WOS:000442807400109 PM 29966369 OA Green Submitted, gold DA 2025-10-02 ER PT J AU Zhu, J Ma, JH Huang, MJ Deng, HX Shi, G AF Zhu, Jiao Ma, Jinhu Huang, Meijuan Deng, Hongxin Shi, Gang TI Emerging delivery strategy for oncolytic virotherapy SO MOLECULAR THERAPY ONCOLOGY LA English DT Review ID MESENCHYMAL STEM-CELLS; DEPENDENT ADENOVIRAL VECTORS; THERAPEUTIC-EFFICACY; SYSTEMIC DELIVERY; STROMAL CELLS; BIOREDUCIBLE POLYMER; ENHANCED ONCOLYSIS; ANTITUMOR EFFICACY; MEDIATED DELIVERY; CELLULAR VEHICLES AB Oncolytic virotherapy represents a promising approach in cancer immunotherapy. The primary delivery method for oncolytic viruses (OVs) is intratumoral injection, which apparently limits their clinical application. For patients with advanced cancer with disseminated metastasis, systemic administration is considered the optimal approach. However, the direct delivery of naked viruses through intravenous injection presents challenges, including rapid clearance by the immune system, inadequate accumulation in tumors, and significant fi cant side effects. Consequently, the development of drug delivery strategies has led to the emergence of various bio-materials serving as viral vectors, thereby improving the anti-tumor efficacy fi cacy of oncolytic virotherapy. This review provides an overview of innovative strategies for delivering OVs, with a focus on nano- particle-based or cell-based delivery systems. Recent pre-clinical and clinical studies are examined to highlight the enhanced efficacy fi cacy of systemic delivery using these novel platforms. In addition, prevalent challenges in current research are briefly fl y discussed, and potential solutions are proposed. C1 [Zhu, Jiao; Ma, Jinhu; Deng, Hongxin; Shi, Gang] Sichuan Univ, West China Hosp, Canc Ctr, Dept Biotherapy, Chengdu 610041, Peoples R China. [Zhu, Jiao; Ma, Jinhu; Deng, Hongxin; Shi, Gang] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Peoples R China. [Zhu, Jiao; Huang, Meijuan] Sichuan Univ, West China Hosp, Canc Ctr, Div Thorac Tumor Multimodal Treatment, Chengdu 610041, Peoples R China. [Zhu, Jiao; Huang, Meijuan] Sichuan Univ, West China Hosp, Canc Ctr, Dept Med Oncol, Chengdu 610041, Peoples R China. C3 Sichuan University; Sichuan University; Sichuan University; Sichuan University RP Deng, HX; Shi, G (corresponding author), Sichuan Univ, West China Hosp, Canc Ctr, Dept Biotherapy, Chengdu 610041, Peoples R China.; Deng, HX; Shi, G (corresponding author), Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Peoples R China. EM denghongx@scu.edu.cn; shig2019@wchscu.edu.cn FU Natural Science Foundation of Sichuan, China [24NSFSC1306]; National Natural Science Foundation of China Program grant [82273315]; The 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University [ZYGD23023] FX This study was funded by the Natural Science Foundation of Sichuan, China (24NSFSC1306) , the National Natural Science Foundation of China Program grant (82273315) , and the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD23023). 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Ther. Oncol. PD JUN 20 PY 2024 VL 32 IS 2 AR 200809 DI 10.1016/j.omton.2024.200809 EA MAY 2024 PG 14 WC Oncology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Research & Experimental Medicine GA D2W5R UT WOS:001294843100001 PM 38845744 OA gold, Green Published DA 2025-10-02 ER PT J AU Russell, SJ Peng, KW Bell, JC AF Russell, Stephen J. Peng, Kah-Whye Bell, John C. TI Oncolytic virotherapy SO NATURE BIOTECHNOLOGY LA English DT Review ID VESICULAR STOMATITIS-VIRUS; HERPES-SIMPLEX-VIRUS; MEDIATED GENE-EXPRESSION; NONLINEAR DOSE-RESPONSE; MESENCHYMAL STEM-CELLS; TUMOR-SPECIFIC DEFECTS; MEASLES-VIRUS; INTRATUMORAL SPREAD; T-CELLS; PHASE-I AB Oncolytic virotherapy is an emerging treatment modality that uses replication-competent viruses to destroy cancers. Recent advances include preclinical proof of feasibility for a single-shot virotherapy cure, identification of drugs that accelerate intratumoral virus propagation, strategies to maximize the immunotherapeutic action of oncolytic viruses and clinical confirmation of a critical viremic threshold for vascular delivery and intratumoral virus replication. The primary clinical milestone has been completion of accrual in a phase 3 trial of intratumoral herpes simplex virus therapy using talimogene laherparepvec for metastatic melanoma. Key challenges for the field are to select 'winners' from a burgeoning number of oncolytic platforms and engineered derivatives, to transiently suppress but then unleash the power of the immune system to maximize both virus spread and anticancer immunity, to develop more meaningful preclinical virotherapy models and to manufacture viruses with orders-of-magnitude higher yields than is currently possible. C1 [Russell, Stephen J.; Peng, Kah-Whye] Mayo Clin, Dept Mol Med, Rochester, MN 55905 USA. [Bell, John C.] Ottawa Hosp Res Inst, Ctr Canc Therapeut, Ottawa, ON, Canada. [Bell, John C.] Jennerex Biotherapeut, San Francisco, CA USA. C3 Mayo Clinic; University of Ottawa; Ottawa Hospital Research Institute RP Russell, SJ (corresponding author), Mayo Clin, Dept Mol Med, Rochester, MN 55905 USA. EM sjr@mayo.edu OI Russell, Stephen/0000-0002-0799-6432 FU Mayo Foundation; Mayo Clinic Comprehensive Cancer Center [CA15083]; National Cancer Institute [CA100634, CA129966, CA118488, CA129193, CA136547, CA136393]; Richard M. Schulze Family Foundation; Ontario Institute for Cancer Research; Terry Fox Foundation; Ottawa Regional Cancer Foundation; US National Institutes of Health; Al and Mary Agnes McQuinn and Minnesota Partnership for Biotechnology FX S.J.R. and K.-W.P. acknowledge funding support from the Mayo Foundation, Mayo Clinic Comprehensive Cancer Center (CA15083), US National Institutes of Health and National Cancer Institute (CA100634, CA129966, CA118488, CA129193, CA136547 and CA136393), Richard M. Schulze Family Foundation, Al and Mary Agnes McQuinn and Minnesota Partnership for Biotechnology. J.C.B. is supported by the Ontario Institute for Cancer Research, the Terry Fox Foundation and the Ottawa Regional Cancer Foundation. 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Biotechnol. PD JUL PY 2012 VL 30 IS 7 BP 658 EP 670 DI 10.1038/nbt.2287 PG 13 WC Biotechnology & Applied Microbiology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biotechnology & Applied Microbiology GA 972QV UT WOS:000306293400025 PM 22781695 DA 2025-10-02 ER PT J AU Hu, Y Sun, YJ Wan, C Dai, XM Wu, SH Lo, PC Huang, J Lovell, JF Jin, HL Yang, KY AF Hu, Yan Sun, Yajie Wan, Chao Dai, Xiaomeng Wu, Shuhui Lo, Pui-Chi Huang, Jing Lovell, Jonathan F. Jin, Honglin Yang, Kunyu TI Microparticles: biogenesis, characteristics and intervention therapy for cancers in preclinical and clinical research SO JOURNAL OF NANOBIOTECHNOLOGY LA English DT Review DE Drug delivery; Extracellular vesicles; Microparticles; Cancer treatment; Immunotherapy ID CELL-DERIVED MICROPARTICLES; MESENCHYMAL STEM-CELLS; EXTRACELLULAR VESICLES; ENDOTHELIAL-CELLS; TISSUE-FACTOR; INTERCELLULAR TRANSFER; ACTIVATED PLATELETS; CIRCULATING MICROPARTICLES; RELEASED MICROVESICLES; ONCOLYTIC ADENOVIRUS AB Extracellular vesicles (EVs), spherical biological vesicles, mainly contain nucleic acids, proteins, lipids and metabolites for biological information transfer between cells. Microparticles (MPs), a subtype of EVs, directly emerge from plasma membranes, and have gained interest in recent years. Specific cell stimulation conditions, such as ultraviolet and X-rays irradiation, can induce the release of MPs, which are endowed with unique antitumor functionalities, either for therapeutic vaccines or as direct antitumor agents. Moreover, the size of MPs (100-1000 nm) and their spherical structures surrounded by a lipid bilayer membrane allow MPs to function as delivery vectors for bioactive antitumor compounds, with favorable phamacokinetic behavior, immunostimulatory activity and biological function, without inherent carrier-specific toxic side effects. In this review, the mechanisms underlying MP biogenesis, factors that influence MP production, properties of MP membranes, size, composition and isolation methods of MPs are discussed. Additionally, the applications and mechanisms of action of MPs, as well as the main hurdles for their applications in cancer management, are introduced. C1 [Hu, Yan; Sun, Yajie; Wan, Chao; Wu, Shuhui; Jin, Honglin; Yang, Kunyu] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Canc Ctr, Wuhan 430022, Peoples R China. [Dai, Xiaomeng] Zhejiang Univ, Affiliated Hosp 1, Coll Med, Dept Med Oncol, Hangzhou, Peoples R China. [Lo, Pui-Chi] City Univ Hong Kong, Dept Biomed Sci, Kowloon, Tat Chee Ave, Hong Kong, Peoples R China. [Huang, Jing; Jin, Honglin] Huazhong Agr Univ, Coll Biomed & Hlth, Wuhan 430070, Peoples R China. [Huang, Jing; Jin, Honglin] Huazhong Agr Univ, Coll Life Sci & Technol, Wuhan 430070, Peoples R China. [Lovell, Jonathan F.] SUNY Buffalo, Univ Buffalo, Dept Biomed Engn, Buffalo, NY 14260 USA. C3 Huazhong University of Science & Technology; Zhejiang University; City University of Hong Kong; Huazhong Agricultural University; Huazhong Agricultural University; State University of New York (SUNY) System; University at Buffalo, SUNY RP Jin, HL; Yang, KY (corresponding author), Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Canc Ctr, Wuhan 430022, Peoples R China. EM jin@hust.edu.cn; yangkunyu@hust.edu.cn RI Yang, Kun/ISA-1094-2023; Sun, Yajie/ABA-8409-2021; Xu, Jialiang/C-2017-2012; Wan, Chao/U-9803-2019 OI Jin, Honglin/0000-0002-4398-9539; Lo, Pui-chi/0000-0002-0315-8538 FU National Natural Science Foundation of China [82073354, 82022040, 81874222]; Hubei Technological Innovation Special Fund [2020BCA068]; Postdoctoral Research Foundation of China [2020M682435] FX This work was financially supported by the National Natural Science Foundation of China (Grant No. 82073354, 82022040, and 81874222), the Hubei Technological Innovation Special Fund (Grant No. 2020BCA068), the Postdoctoral Research Foundation of China (2020M682435). 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Nanobiotechnol. PD APR 13 PY 2022 VL 20 IS 1 AR 189 DI 10.1186/s12951-022-01358-0 PG 28 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 0O5AR UT WOS:000783539200002 PM 35418077 OA Green Published, gold DA 2025-10-02 ER PT J AU Shah, K AF Shah, Khalid TI Stem cell-based therapies for tumors in the brain: are we there yet? SO NEURO-ONCOLOGY LA English DT Review DE brain tumors; glioblastoma (GBM); receptors; stem cells; therapeutics ID MESENCHYMAL STROMAL CELLS; NEURAL PROGENITOR CELLS; SUICIDE GENE-THERAPY; GLIOMA-CELLS; ONCOLYTIC ADENOVIRUS; INTRANASAL DELIVERY; INTRACRANIAL GLIOMA; CYTOSINE DEAMINASE; CANCER; GROWTH AB Advances in understanding adult stem cell biology have facilitated the development of novel cell-based therapies for cancer. Recent developments in conventional therapies (eg, tumor resection techniques, chemotherapy strategies, and radiation therapy) for treating both metastatic and primary tumors in the brain, particularly glioblastoma have not resulted in a marked increase in patient survival. Preclinical studies have shown that multiple stem cell types exhibit inherent tropism and migrate to the sites of malignancy. Recent studies have validated the feasibility potential of using engineered stem cells as therapeutic agents to target and eliminate malignant tumor cells in the brain. This review will discuss the recent progress in the therapeutic potential of stem cells for tumors in the brain and also provide perspectives for future preclinical studies and clinical translation. C1 [Shah, Khalid] Harvard Med Sch, Massachusetts Gen Hosp, Stem Cell Therapeut & Imaging Program, Boston, MA USA. [Shah, Khalid] Harvard Med Sch, Massachusetts Gen Hosp, Mol Neurotherapy & Imaging Lab, Boston, MA USA. [Shah, Khalid] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Shah, Khalid] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Shah, Khalid] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. C3 Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Harvard University RP Shah, K (corresponding author), 5403,Bldg 149,13th St, Charlestown, MA 01810 USA. EM kshah@mgh.harvard.edu RI Shah, Amy/AAB-4631-2020 FU [R01CA138922]; [R01CA173077] FX This work was supported by R01CA138922 and R01CA173077. 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10.1158/1541-7786.MCR-08-0146 Zhao Y, 2012, GENE THER, V19, P189, DOI 10.1038/gt.2011.82 Zomer HD, 2015, STEM CELLS CLONING, V8, P125, DOI 10.2147/SCCAA.S88036 NR 145 TC 52 Z9 59 U1 1 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD AUG PY 2016 VL 18 IS 8 BP 1066 EP 1078 DI 10.1093/neuonc/now096 PG 13 WC Oncology; Clinical Neurology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Neurosciences & Neurology GA DV9TT UT WOS:000383285800005 PM 27282399 OA Bronze DA 2025-10-02 ER PT J AU Mercer-Smith, AR Findlay, IA Bomba, HN Hingtgen, SD AF Mercer-Smith, Alison R. Findlay, Ingrid A. Bomba, Hunter N. Hingtgen, Shawn D. TI Intravenously Infused Stem Cells for Cancer Treatment SO STEM CELL REVIEWS AND REPORTS LA English DT Article DE Intravenous therapy; Neural stem cells; Mesenchymal stem cells; Cell-based drug delivery; Oncolytic viruses; Nanoparticle-loaded cells ID PEGYLATED LIPOSOMAL DOXORUBICIN; UMBILICAL-CORD BLOOD; MARROW STROMAL CELLS; PHASE-III TRIAL; BONE-MARROW; CYTOSINE DEAMINASE; ENHANCED PERMEABILITY; ONCOLYTIC ADENOVIRUS; ANTITUMOR-ACTIVITY; MEASLES-VIRUS AB Despite the recent influx of immunotherapies and small molecule drugs to treat tumors, cancer remains a leading cause of death in the United States, in large part due to the difficulties of treating metastatic cancer. Stem cells, which are inherently tumoritropic, provide a useful drug delivery vehicle to target both primary and metastatic tumors. Intravenous infusions of stem cells carrying or secreting therapeutic payloads show significant promise in the treatment of cancer. Stem cells may be engineered to secrete cytotoxic products, loaded with oncolytic viruses or nanoparticles containing small molecule drugs, or conjugated with immunotherapies. Herein we describe these preclinical and clinical studies, discuss the distribution and migration of stem cells following intravenous infusion, and examine both the limitations of and the methods to improve the migration and therapeutic efficacy of tumoritropic, therapeutic stem cells. C1 [Mercer-Smith, Alison R.; Findlay, Ingrid A.; Bomba, Hunter N.; Hingtgen, Shawn D.] Univ N Carolina, UNC Eshelman Sch Pharm, Div Pharmacoengn & Mol Pharmaceut, Chapel Hill, NC 27599 USA. [Hingtgen, Shawn D.] Univ N Carolina, Dept Neurosurg, Chapel Hill, NC 27599 USA. C3 University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina; University of North Carolina Chapel Hill RP Hingtgen, SD (corresponding author), Univ N Carolina, UNC Eshelman Sch Pharm, Div Pharmacoengn & Mol Pharmaceut, Chapel Hill, NC 27599 USA.; Hingtgen, SD (corresponding author), Univ N Carolina, Dept Neurosurg, Chapel Hill, NC 27599 USA. EM hingtgen@email.unc.edu RI Bomba, Hunter/KIL-6276-2024 OI Mercer-Smith, Alison/0000-0001-9571-2219 FU Eshelman Institute for Innovation; National Cancer Institute of the National Institutes of Health [F30CA243270] FX This work was supported by Eshelman Institute for Innovation and the National Cancer Institute of the National Institutes of Health under Award Number F30CA243270. 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Rep. PD DEC PY 2021 VL 17 IS 6 BP 2025 EP 2041 DI 10.1007/s12015-021-10192-0 EA JUN 2021 PG 17 WC Cell & Tissue Engineering; Cell Biology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Research & Experimental Medicine GA XB0RU UT WOS:000662853600001 PM 34138421 OA Green Submitted DA 2025-10-02 ER EF