Breathing new life into T-cell receptor-engineered T-cell therapy in solid tumors: enhancing strategies to expand the universality of precision therapy.

Abstract

Adoptive T-cell transfer therapy (ACT) has significantly propelled the advancement of tumor immunotherapy. Among various strategies targeting solid tumors, the T-cell receptor (TCR)-engineered T-cell (TCR-T cell) therapy has emerged as a highly promising approach, exhibiting an expanded therapeutic window across diverse patient populations and superior tumoricidal activity in certain solid malignancies compared with chimeric antigen receptor T cell (CAR-T) and tumor-infiltrating T cells/lymphocyte (TIL) therapies. However, its clinical efficacy remains constrained. In this paper, we introduce the limitations and challenges faced by TCR-T cells in solid tumor treatment, and summarize recent efforts overcoming these limitations and translating TCR-T cell therapies into clinical application. Furthermore, their current status and effectiveness in clinical solid tumor patients were analyzed. We expect that the precision therapies of TCR-T cells, with the support of high-affinity TCRs and a diverse array of target antigens, multimodal synergistic therapy strategies and efficient in vitro production processes, will benefit a wider patient population, thus revealing new clinical application potential.