CRISPR/Cas9 and CAR-T cell, collaboration of two revolutionary technologies in cancer immunotherapy, an instruction for successful cancer treatment

Hum Immunol. 2018 Dec;79(12):876-882. doi: 10.1016/j.humimm.2018.09.007. Epub 2018 Sep 24.

Abstract

Clustered regularly interspaced short palindromic repeats/CRISPR associated nuclease9 (CRISPR/Cas9) technology, an acquired immune system in bacteria and archaea, has provided a new tool for accurately genome editing. Using only a single nuclease protein in complex with 2 short RNA as a site-specific endonuclease made it a simple and flexible genome editing tool to target nearly any genomic locus. Due to recent developments in therapeutic engineered T cell and effective responses of CD19-directed chimeric antigen receptor T cells (CART19) in patients with B-cell leukemia and lymphoma, adoptive T cell immunotherapy, particularly CAR-T cell therapy became a rapidly growing field in cancer therapy and recently Kymriah and Yescarta (CD19-directed CAR-T cells) were approved by FDA. Therefore, the combination of CRISPR/Cas9 technology as a genome engineering tool and CAR-T cell therapy (engineered T cells that express chimeric antigen receptors) may lead to further improvement in efficiency and safety of CAR-T cells. This article reviews mechanism and therapeutic application of CRISPR/Cas9 technology, accuracy of this technology, cancer immunotherapy by CAR T cells, the application of CRISPR technology for the production of universal CAR T cells, improving their antitumor efficacy, and biotech companies that invested in CRISPR technology for CAR-T cell therapy.

Keywords: Biotechnology companies; CAR T cell; CRISPR/Cas9 technology; Cancer immunotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • CRISPR-Cas Systems*
  • Gene Editing / methods*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / immunology*
  • Receptors, Chimeric Antigen / metabolism
  • Reproducibility of Results
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Treatment Outcome

Substances

  • Receptors, Chimeric Antigen