Page 30 - ARNM-1-2

Advances in Radiotherapy
& Nuclear Medicine FAP-targeted RLT in cancer

Several pre-clinical studies have investigated the efficacy robust immune response and improved antitumor efficacy.
of TRT combined with immunotherapy, consistently Therefore, the utilization of FAP-targeted RLT, either alone
demonstrating the capacity of this combination to or in combination with immunotherapy or chemotherapy,
enhance the immune response, improve the efficacy of holds significant promise for the future of cancer treatment.
immunotherapy, and achieve superior overall outcomes Nonetheless, comprehensive clinical trials will be essential
compared to the use of either immunotherapy or TRT in the future to ascertain the effectiveness of combining
alone [66,67] . Choi et al. conducted an investigation into the FAP-targeted RLT with immunotherapy or chemotherapy.
efficacy of TRT ( Lu-LLP2A) when combined with dual
177
immunotherapy (anti-PD-1 + anti-CTLA-4 or anti-PD-L1 Acknowledgments
+ anti-CTLA-4) using a murine melanoma model . In None.
[67]
a separate study, Chen et al. explored the optimal timing
and potential mechanisms of TRT ( Lu-EB-RGD) when Funding
177
administered in conjunction with immunotherapy (anti- This work was funded by the National Natural Science
PD-L1 antibody) in a mouse model of colon cancer . Foundation of China (Grant number: 82071961), Fujian
[66]
Czernin et al. confirmed that the combination of TRT Research and Training Grants for Young and Middle-aged
( Ac-PSMA617) with immunotherapy (anti-PD-1 Leaders in Healthcare, Key Scientific Research Program
225
antibody) led to synergistic improvements in therapeutic for Yong Scholars in Fujian (Grant number: 2021ZQNZD
outcomes in C57BL/6 mouse models of prostate cancer . 016), Fujian Natural Science Foundation for Distinguished
[68]
Furthermore, a recent report by Esfahani et al. reported Yong Scholars (Grant number: 2022D005), Natural
improved treatment responses through the combination of Science Foundation of Fujian Province (Grant number:
PRRT ( Lu-DOTATATE) and immunotherapy (anti-PD-1 2020J011220), Key Medical and Health Projects in Xiamen
177
antibody) in NET-bearing mice . These collective (Grant number: 3502Z20209002), Xiamen Key Laboratory
[69]
findings underscore the potential for a synergistic effect of Radiopharmaceuticals, Xiamen Key Laboratory of
when TRT and immunotherapy are combined. A previous Radiation Oncology, Xiamen Clinical Research Center for
study identified that the depletion of FAP-positive CAFs Head and Neck Cancer, and 2021 National Clinical Key
enhanced the antitumor effect of PD-L1 immunotherapy. Specialty (Oncology, Grant number: 3210013).
In an autochthonous model of pancreatic ductal
adenocarcinoma, T-cell infiltration has been demonstrated Conflict of interest
to reduce cancer cell growth . This reduction in cancer The authors declare that they have no conflicts of interest.
[70]
cells suggests that the combination of FAP-targeted RLT
with immunotherapy has the potential to enhance the Author contributions
immune response, thereby improving antitumor efficacy.
However, only one pre-clinical study, conducted by Conceptualization: Haojun Chen, Qin Lin
Zboralski et al., has investigated whether the combination Writing – original draft: Yizhen Pang, Liang Zhao
of FAP-targeted RLT and immunotherapy could generate a Writing – review & editing: Jianhao Chen, Weizhi Xu, Jiayu
synergistic effect, resulting in a treatment outcome where 1 Cai
+ 1 >2 . The results of this pre-clinical study demonstrated Ethics approval and consent to participate
[71]
that FAP-targeted RLT enhanced anti-PD-1-mediated
inhibition of tumor growth by modulating the TME and Not applicable.
increasing the recruitment of tumor-infiltrating CD8+ T
cells. These findings provide a compelling rationale for Consent for publication
conducting clinical studies involving a combination of FAP- Not applicable.
targeted RLT and immunotherapy in FAP-positive tumors.
By modulating the TME and enhancing the recruitment Availability of data
of tumor-infiltrating CD8+ T cells, this approach offers The datasets used and/or analyzed during the present
promising prospects for improved therapeutic outcomes. study are available from the corresponding author upon
7. Conclusion reasonable request.
FAP-targeted RLT has shown promising results in clinical References
and pre-clinical studies. Furthermore, combining FAP- 1. Kim KJ, Kim KJ, Choi J, et al., 2023, Linear association
targeted RLT with immunotherapy has demonstrated between radioactive iodine dose and second primary
synergistic effects in pre-clinical studies, leading to a more malignancy risk in thyroid cancer. J Natl Cancer Inst,

Volume 1 Issue 2 (2023) 9 https://doi.org/10.36922/arnm.1667