Genetical engineering for NK and T cell immunotherapy with CRISPR/Cas9 technology: Implications and challenges

Cell Immunol. 2021 Nov:369:104436. doi: 10.1016/j.cellimm.2021.104436. Epub 2021 Sep 1.

Abstract

Immunotherapy has become one of the most promising strategies in cancer therapies. Among the therapeutic alternatives, genetically engineered NK/T cell therapies have emerged as powerful and innovative therapeutic modalities for cancer patients with precise targeting and impressive efficacy. Nonetheless, this approach still faces multiple challenges, such as immunosuppressive tumor microenvironment, exhaustion of immune effector cells in tumors, off-target effects manufacturing complexity, and poor infiltration of effector cells, all of which need to be overcome for further utilization to cancers. Recently, CRISPR/Cas9 genome editing technology, with the goal of enhancing the efficacy and increasing the availability of engineered effector cell therapies, has shown considerable potential in the novel strategies and options to overcome these limitations. Here we review the current progress of the applications of CRISPR in cancer immunotherapy. Furthermore, we discuss issues related to the NK/T cell applications, gene delivery methods, efficiency, challenges, and implications of CRISPR/Cas9.

Keywords: CRISPR/Cas9; Cancer; Genome editing; Immunotherapy; NK/T cell.

Publication types

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

MeSH terms

  • Animals
  • CRISPR-Cas Systems*
  • Gene Editing / methods*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Killer Cells, Natural / transplantation*
  • Receptors, Chimeric Antigen / therapeutic use*
  • T-Lymphocytes / transplantation*

Substances

  • Receptors, Chimeric Antigen