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Review
. 2021 May 20:9:674467.
doi: 10.3389/fcell.2021.674467. eCollection 2021.

CRISPR/Cas9 Gene-Editing in Cancer Immunotherapy: Promoting the Present Revolution in Cancer Therapy and Exploring More

Xuejin Ou  1   2 , Qizhi Ma  2 , Wei Yin  3 , Xuelei Ma  1 , Zhiyao He  1   4
Affiliations
Review

CRISPR/Cas9 Gene-Editing in Cancer Immunotherapy: Promoting the Present Revolution in Cancer Therapy and Exploring More

Xuejin Ou et al. Front Cell Dev Biol. .

Abstract

In recent years, immunotherapy has showed fantastic promise in pioneering and accelerating the field of cancer therapy and embraces unprecedented breakthroughs in clinical practice. The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (CRISPR-Cas9) system, as a versatile gene-editing technology, lays a robust foundation to efficiently innovate cancer research and cancer therapy. Here, we summarize recent approaches based on CRISPR/Cas9 system for construction of chimeric antigen receptor T (CAR-T) cells and T cell receptor T (TCR-T) cells. Besides, we review the applications of CRISPR/Cas9 in inhibiting immune checkpoint signaling pathways and highlight the feasibility of CRISPR/Cas9 based engineering strategies to screen novel cancer immunotherapy targets. Conclusively, we discuss the perspectives, potential challenges and possible solutions in this vivid growing field.

Keywords: CAR-T; CRISPR/Cas9; TCR-T; immunotherapy; tumor-infiltrating lymphocytes.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The application of CRISPR/Cas9 system in editing CAR-T cells: Knocking out endogenous TCR locus and MHC-1 molecule to generate universal CAR-T cells.
FIGURE 2
FIGURE 2
The application of CRISPR/Cas9 system in editing CAR-T cells: Knocking out inhibitory molecules to enhance function of CAR-T cells.
FIGURE 3
FIGURE 3
Application of CRISPR/Cas9 system in engineered T cell receptor (TCR)-based adoptive T cell therapy: Knocking out endogenous TCRs to avoid mixed TCR dimer formation and improve transduced TCR expression.
See this image and copyright information in PMC

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