Cancer Therapy With TCR-Engineered T Cells: Current Strategies, Challenges, and Prospects

Front Immunol. 2022 Mar 3;13:835762. doi: 10.3389/fimmu.2022.835762. eCollection 2022.


To redirect T cells against tumor cells, T cells can be engineered ex vivo to express cancer-antigen specific T cell receptors (TCRs), generating products known as TCR-engineered T cells (TCR T). Unlike chimeric antigen receptors (CARs), TCRs recognize HLA-presented peptides derived from proteins of all cellular compartments. The use of TCR T cells for adoptive cellular therapies (ACT) has gained increased attention, especially as efforts to treat solid cancers with ACTs have intensified. In this review, we describe the differing mechanisms of T cell antigen recognition and signal transduction mediated through CARs and TCRs. We describe the classes of cancer antigens recognized by current TCR T therapies and discuss both classical and emerging pre-clinical strategies for antigen-specific TCR discovery, enhancement, and validation. Finally, we review the current landscape of clinical trials for TCR T therapy and discuss what these current results indicate for the development of future engineered TCR approaches.

Keywords: CAR; T cell receptor; TCR; TCR T; TCR-engineered T cells; adoptive cell therapy; chimeric antigen receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Humans
  • Immunotherapy, Adoptive / methods
  • Neoplasms*
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen* / genetics
  • Receptors, Chimeric Antigen* / metabolism
  • T-Lymphocytes


  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen