靶向新抗原的 TCR 工程化 T 细胞免疫治疗：当前进展与挑战

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.