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

Estelle Baulu (1) , Célia Gardet (1) , Nicolas Chuvin , Stéphane Depil (1)

1 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon

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.

Domaines: Cancer

Estelle Baulu, Célia Gardet, Nicolas Chuvin, Stéphane Depil. TCR-engineered T cell therapy in solid tumors: State of the art and perspectives. Science Advances , 2023, 9 (7), ⟨10.1126/sciadv.adf3700⟩. ⟨hal-04115921⟩