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Gene & Protein in Disease Genetically engineered T cells in cancer immunotherapy

high affinity [102,103] . Although TCR-T cell immunotherapy We believe the accumulation of findings from basic
has shown some clinical efficacy in most treated patients, research and clinical translation will hasten and support
some obstacles remain to be overcome to realize the real the approval of more gene-engineered T cell products for
promise of TCR-T cells therapy. Some nonresponsive clinical applications.
patients lack in vivo persistence of T cell infusion in
clinical trials, suggesting that TCR-T cells require Acknowledgments
additional support to improve their persistence in vivo [104] . None.
T cell infiltration into the tumor is not observed in some
patients with late recurrence, and the infused TCR-T cells Funding
confront with an unfavorable immunosuppressive tumor This study was supported by grants from Healthy
microenvironment. In general, the application of TCR-T Talents Project of Henan Province (YXKC2020052)
cells is still a challenge in many areas, including targeted and the National Natural Science Foundation of China
immunotoxicity caused by normal tissues, low transient (No.8210286, No. 81771781, No. 81872333).
efficiency of TCR in engineered T cells, exhaustion and
dysfunction of T cells, tumor immune escape and the lack Conflict of interest
of effective tumor-specific antigens in most patients with
tumors [105] . Therefore, overcoming these challenges is key The authors declare that they have no competing interests.
to achieving greater clinical success in the future. Author contributions

8. Improving the safety and efficacy of Supervision: Yi Zhang
TCR-T cell therapy Writing – original draft: Xinfeng Chen, Shasha Liu
Writing – review & editing: Xinfeng Chen, Shasha Liu,
The persistence and expansion of antigen specific T cells in Zhen Zhang
vivo are related to the response to TCR-T cell therapy [98,106] .
The function of tumor antigen-specific T cells expressing References
exhaustion marker in the tumor is impaired [107] . Exhaustion
limits the anti-tumor immune response of T cells, and 1. Neelapu SS, Dickinson M, Munoz J, et al., 2022, Axicabtagene
combination of immune checkpoint inhibitors with ciloleucel as first-line therapy in high-risk large B-cell
lymphoma: The phase 2 ZUMA-12 trial. Nat Med, 28(4):
TCR-T cells could produce synergistic anti-tumor effect. 735–742.
Like in CAR-T cells, IL-7 and CCL19 were constructed
into TCR-T cells to generate potent and durable anti- https://doi.org/10.1038/s41591-022-01731-4
tumor immunity when synergizing with PD-1 blockade 2. Locke FL, Miklos DB, Jacobson CA, et al., 2022, Axicabtagene
therapy [108] . Co-expressing PD1-41BB-modified PRAME- ciloleucel as second-line therapy for large B-cell lymphoma.
specific TCR-T cells produced strong anti-tumor reactivity N Engl J Med, 386(7): 640–654.
in an animal model [109] . After identifying TCR sequences https://doi.org/10.1056/NEJMoa2116133
that specifically targeting neoantigens, TCR-T cells were
reconstructed so that they are equipped with the potential 3. Mullard A, 2021, FDA approves first BCMA-targeted CAR-T
anti-tumor ability [110] . cell therapy. Nat Rev Drug Discov, 20(5): 332.
https://doi.org/10.1038/d41573-021-00063-1
9. Outlooks
4. Greenbaum U, Dumbrava EI, Biter AB, et al., 2021,
The remarkable success of adoptive T cell therapy for Engineered T-cell receptor T cells for cancer immunotherapy.
hematological tumors (B-ALL, B-cell lymphoma, and Cancer Immunol Res, 9(11): 1252–1261.
MM) makes CAR-T cells a promising therapeutic method https://doi.org/10.1158 / 2326-6066.CIR-21-0269
for tumors, and promotes the rapid development of gene- 5. Robbins PF, Morgan RA, Feldman SA, et al., 2011, Tumor
modified T cell therapy. However, there are significant regression in patients with metastatic synovial cell sarcoma
differences in anti-tumor mechanisms between CAR-T and melanoma using genetically engineered lymphocytes
cells and TCR-T cells, such as structure, target, affinity, reactive with NY-ESO-1. J Clin Oncol, 29(7): 917–924.
costimulatory molecule, and HLA limitation. They have https://doi.org/10.1200/JCO.2010.32.2537
the same issues, including toxicity, poor efficacy, poor
infiltration, and immunosuppressive microenvironment in 6. Schank TE, Hassel JC, 2022, Tebentafusp for the treatment
the treatment of solid tumors. The optimization of CAR or of metastatic uveal melanoma. Future Oncol, 18(11):
TCR structure will further improve its efficacy and safety, 1303–1311.
and facilitate the development of solid tumor treatment. https://doi.org/10.2217/fon-2021-1260

Volume 1 Issue 1 (2022) 9 https://doi.org/10.36922/gpd.v1i1.114