Engineering Strategies to Enhance TCR-Based Adoptive T Cell Therapy

Cells. 2020 Jun 18;9(6):1485. doi: 10.3390/cells9061485.

Abstract

T cell receptor (TCR)-based adoptive T cell therapies (ACT) hold great promise for the treatment of cancer, as TCRs can cover a broad range of target antigens. Here we summarize basic, translational and clinical results that provide insight into the challenges and opportunities of TCR-based ACT. We review the characteristics of target antigens and conventional αβ-TCRs, and provide a summary of published clinical trials with TCR-transgenic T cell therapies. We discuss how synthetic biology and innovative engineering strategies are poised to provide solutions for overcoming current limitations, that include functional avidity, MHC restriction, and most importantly, the tumor microenvironment. We also highlight the impact of precision genome editing on the next iteration of TCR-transgenic T cell therapies, and the discovery of novel immune engineering targets. We are convinced that some of these innovations will enable the field to move TCR gene therapy to the next level.

Keywords: CRISPR; adoptive T cell therapy; avidity; cancer immunotherapy; chimeric antigen receptor; chimeric receptors; engineered T cells; gene editing; transgenic TCR; tumor microenvironment.

Publication types

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

MeSH terms

  • Biomedical Engineering
  • Cell Engineering
  • Cell- and Tissue-Based Therapy / adverse effects
  • Cell- and Tissue-Based Therapy / methods*
  • Cell- and Tissue-Based Therapy / trends
  • Gene Editing
  • Genetic Therapy
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / methods*
  • Immunotherapy, Adoptive / trends
  • Lymphocyte Activation
  • Molecular Targeted Therapy
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Safety
  • Synthetic Biology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation*
  • Translational Research, Biomedical
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta