Advancing chimeric antigen receptor T cell therapy with CRISPR/Cas9.
10.1007/s13238-017-0410-x
- Author:
Jiangtao REN
1
;
Yangbing ZHAO
2
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.
- Publication Type:Journal Article
- Keywords:
CRISPR/Cas9;
T lymphocytes;
adoptive immunotherapy;
chimeric antigen receptor;
gene therapy
- MeSH:
Animals;
Clustered Regularly Interspaced Short Palindromic Repeats;
immunology;
Gene Editing;
methods;
Humans;
Immunotherapy;
methods;
Receptors, Antigen, T-Cell;
genetics;
immunology;
Recombinant Fusion Proteins;
genetics;
immunology
- From:
Protein & Cell
2017;8(9):634-643
- CountryChina
- Language:English
-
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.