Cancer immunotherapy with lymphocytes genetically engineered with T cell receptors for solid cancers

Adoptive transfer of T cells genetically engineered with chimeric antigen receptors (CAR-T cells) have proven to be highly effective for treating CD19⁺ B cell-derived hematologic malignancies. However, due to the lack of ideal tumor surface antigens, CAR-T cell therapy has limited success in treating solid tumors. T cells genetically engineered with T cell receptors (TCR-T cells) recognize intracellular and cell-surface antigens in the context of major histocompatibility complex (MHC) presentation and thus have the potential to access much more target antigens than CAR-T cells, providing great promise in treating solid tumors. There is an increasing interest in the application of TCR-T cell therapy for solid tumors, and fifty-six clinical trials are undergoing worldwide to confirm its validity. In this review, we summarize the recent progress in clinical studies of TCR-T cell therapy, describe strategies in the preparation and characterization of TCR-T cells, focusing on antigen selection, TCR isolation and methods to further enhance the potency of adoptively transferred cells.