TCR-engineered T cell therapy in solid tumors: State of the art and perspectives

T cell engineering has changed the landscape of cancer immunotherapy. Chimeric antigen receptor T cells have demonstrated a remarkable efficacy in the treatment of B cell malignancies in hematology. However, their clinical impact on solid tumors has been modest so far. T cells expressing an engineered T cell receptor (TCR-T cells) represent a promising therapeutic alternative. The target repertoire is not limited to membrane proteins, and intrinsic features of TCRs such as high antigen sensitivity and near-to-physiological signaling may improve tumor cell detection and killing while improving T cell persistence. In this review, we present the clinical results obtained with TCR-T cells targeting different tumor antigen families. We detail the different methods that have been developed to identify and optimize a TCR candidate. We also discuss the challenges of TCR-T cell therapies, including toxicity assessment and resistance mechanisms. Last, we share some perspectives and highlight future directions in the field.

Automated summary

T cell engineering has revolutionized cancer immunotherapy. Chimeric antigen receptor T cells have shown great efficacy in treating B cell malignancies, while T cells expressing engineered T cell receptors (TCR-T cells) offer a promising therapeutic alternative for solid tumors. This review summarizes clinical results and methods for identifying and optimizing TCR candidates, discusses challenges such as toxicity assessment and resistance mechanisms, and highlights future directions in the field.