Building Potent Chimeric Antigen Receptor T Cells With CRISPR Genome Editing

Front Immunol. 2019 Mar 19:10:456. doi: 10.3389/fimmu.2019.00456. eCollection 2019.

Abstract

Chimeric antigen receptor (CAR) T cells have shown great promise in the treatment of hematological and solid malignancies. However, despite the success of this field, there remain some major challenges, including accelerated T cell exhaustion, potential toxicities, and insertional oncogenesis. To overcome these limitations, recent advances in CRISPR technology have enabled targetable interventions of endogenous genes in human CAR T cells. These CRISPR genome editing approaches have unleashed the therapeutic potential of CAR T cell therapy. Here, we summarize the potential benefits, safety concerns, and difficulties in the generation of gene-edited CAR T cells using CRISPR technology.

Keywords: CAR T; CRISPR; cancer; chimeric antigen receptor; gene editing; immunotherapy.

Publication types

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

MeSH terms

  • CRISPR-Cas Systems*
  • Gene Editing / methods*
  • Graft vs Host Disease / etiology
  • Humans
  • Immunotherapy, Adoptive / adverse effects*
  • Immunotherapy, Adoptive / trends
  • Neoplasms / therapy*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology
  • Receptors, Chimeric Antigen / genetics*
  • T-Lymphocytes / immunology*

Substances

  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Chimeric Antigen