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

Sci Adv. 2023 Feb 15;9(7):eadf3700. doi: 10.1126/sciadv.adf3700. Epub 2023 Feb 15.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Antigens, Neoplasm
  • Cell- and Tissue-Based Therapy
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Neoplasms* / metabolism
  • Receptors, Antigen, T-Cell / metabolism

Substances

  • Receptors, Antigen, T-Cell
  • Antigens, Neoplasm