CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells
- Author:
Zhang YONGPING
1
;
Zhang XINGYING
;
Cheng CHEN
;
Mu WEI
;
Liu XIAOJUAN
;
Li NA
;
Wei XIAOFEI
;
Liu XIANG
;
Xia CHANGQING
;
Wang HAOYI
Author Information
1. Department of Hematology
- Keywords:
CAR-T;
CRISPR-Cas9;
LAG-3
- From:
Frontiers of Medicine
2017;11(4):554-562
- CountryChina
- Language:Chinese
-
Abstract:
T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advanced refractory B cell malignancy.However,many challenges remain in extending its application toward the treatment of solid tumors.The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CAR-T efficacy.One negative regulator of T cell activity is lymphocyte activation gene-3 (LAG-3).We successfully generated LAG-3 knockout T and CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture.LAG-3 knockout CAR-T cells displayed robust antigen-specific antitumor activity in cell culture and in murine xenograft model,which is comparable to standard CAR-T cells.Our study demonstrates an efficient approach to silence immune checkpoint in CAR-T cells via gene editing.
