The Anticancer Potential of T Cell Receptor-Engineered T Cells

Trends Cancer. 2021 Jan;7(1):48-56. doi: 10.1016/j.trecan.2020.09.002. Epub 2020 Sep 26.

Abstract

Adoptively transferred T cell receptor (TCR)-transgenic T cells (TCR-T cells) are not restricted by cell surface expression of their targets and are therefore poised to become a main pillar of cellular cancer immunotherapies. Addressing clinical and laboratory data, we discuss emerging features for the efficient deployment of novel TCR-T therapies, such as selection of ideal TCRs targeting validated epitopes with well-characterized cancer cell expression and processing, enhancing TCR-T effector function, trafficking, expansion, persistence, and memory formation by strategic selection of substrate cells, and gene-engineering with synthetic co-stimulatory circuits. Overall, a better understanding of the relevant mechanisms of action and resistance will help prioritize the vast array of potential TCR-T optimizations for future clinical products.

Keywords: TCR-T; cancer immunotherapy; engineered T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Autoantigens / genetics
  • Autoantigens / immunology
  • Autoantigens / metabolism
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Mice
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Protein Engineering
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Cytotoxic / transplantation*
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • T-Lymphocytes, Helper-Inducer / transplantation*
  • Treatment Outcome

Substances

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