Title |
CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells
|
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Published in |
Frontiers of Medicine, June 2017
|
DOI | 10.1007/s11684-017-0543-6 |
Pubmed ID | |
Authors |
Yongping Zhang, Xingying Zhang, Chen Cheng, Wei Mu, Xiaojuan Liu, Na Li, Xiaofei Wei, Xiang Liu, Changqing Xia, Haoyi Wang |
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 Tcell activity is lymphocyte activation gene-3 (LAG-3). We successfully generated LAG-3 knockout Tand 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 171 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 31 | 18% |
Student > Bachelor | 27 | 16% |
Researcher | 23 | 13% |
Student > Master | 15 | 9% |
Other | 8 | 5% |
Other | 18 | 11% |
Unknown | 49 | 29% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 37 | 22% |
Immunology and Microbiology | 29 | 17% |
Agricultural and Biological Sciences | 19 | 11% |
Medicine and Dentistry | 15 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 7 | 4% |
Other | 12 | 7% |
Unknown | 52 | 30% |