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Protein Cell. 2017 Sep;8(9):634-643. doi: 10.1007/s13238-017-0410-x. Epub 2017 Apr 22.

Advancing chimeric antigen receptor T cell therapy with CRISPR/Cas9.

Author information

1
Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104-5156, USA.
2
Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104-5156, USA. Yangbing@upenn.edu.

Abstract

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (CRISPR/Cas9) system, an RNA-guided DNA targeting technology, is triggering a revolution in the field of biology. CRISPR/Cas9 has demonstrated great potential for genetic manipulation. In this review, we discuss the current development of CRISPR/Cas9 technologies for therapeutic applications, especially chimeric antigen receptor (CAR) T cell-based adoptive immunotherapy. Different methods used to facilitate efficient CRISPR delivery and gene editing in T cells are compared. The potential of genetic manipulation using CRISPR/Cas9 system to generate universal CAR T cells and potent T cells that are resistant to exhaustion and inhibition is explored. We also address the safety concerns associated with the use of CRISPR/Cas9 gene editing and provide potential solutions and future directions of CRISPR application in the field of CAR T cell immunotherapy. As an integration-free gene insertion method, CRISPR/Cas9 holds great promise as an efficient gene knock-in platform. Given the tremendous progress that has been made in the past few years, we believe that the CRISPR/Cas9 technology holds immense promise for advancing immunotherapy.

KEYWORDS:

CRISPR/Cas9; T lymphocytes; adoptive immunotherapy; chimeric antigen receptor; gene therapy

PMID:
28434148
PMCID:
PMC5563282
DOI:
10.1007/s13238-017-0410-x
[Indexed for MEDLINE]
Free PMC Article

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