2017, Volume 11, Issue 4
Frontiers of Medicine >> 2017, Volume 11, Issue 4 doi: 10.1007/s11684-017-0543-6
CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells
1. Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
2. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing100190, China.
3. University of Chinese Academy of Sciences, Beijing 100049, China.
4. Graduate School, University of Science and Technology of China, Hefei 230026, China.
5. Department of Pathology, Immunology and Laboratory Medicine, University of Florida, FL 32611, USA.
6. Beijing Cord Blood Bank, Beijing100176, China
Next Previous
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.
Keywords
CAR-T ; CRISPR-Cas9 ; LAG-3
京公网安备 11010502051620号
