Neoantigen-targeted TCR-engineered T cell immunotherapy: current advances and challenges.

Biomark Res

Liver Cancer Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Published: December 2023

Adoptive cell therapy using T cell receptor-engineered T cells (TCR-T) is a promising approach for cancer therapy with an expectation of no significant side effects. In the human body, mature T cells are armed with an incredible diversity of T cell receptors (TCRs) that theoretically react to the variety of random mutations generated by tumor cells. The outcomes, however, of current clinical trials using TCR-T cell therapies are not very successful especially involving solid tumors. The therapy still faces numerous challenges in the efficient screening of tumor-specific antigens and their cognate TCRs. In this review, we first introduce TCR structure-based antigen recognition and signaling, then describe recent advances in neoantigens and their specific TCR screening technologies, and finally summarize ongoing clinical trials of TCR-T therapies against neoantigens. More importantly, we also present the current challenges of TCR-T cell-based immunotherapies, e.g., the safety of viral vectors, the mismatch of T cell receptor, the impediment of suppressive tumor microenvironment. Finally, we highlight new insights and directions for personalized TCR-T therapy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10690996PMC
http://dx.doi.org/10.1186/s40364-023-00534-0DOI Listing

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