A novel AXL chimeric antigen receptor endows T cells with anti-tumor effects against triple negative breast cancers

作者：Wei, Jing; Sun, Huiyan; Zhang, Aimei; Wu, Xuejie; Li, Yuxiang; Liu, Jiawei; Duan, Yanting; Xiao, Fengjun; Wang, Hua; Lv, Ming^*; Wang, Lisheng^*; Wu, Chutse^*

来源：Cellular Immunology, 2018, 331: 49-58.

DOI：10.1016/j.cellimm.2018.05.004

• CAR-T cells
• AXL
• Breast cancer

Identifying targets for chimeric antigen receptor-modulated T lymphocyte (CAR-T) therapy against solid tumors is an urgent problem to solve. In this study, we showed for the first time that the receptor tyrosine kinase, AXL, is overexpressed in various tumor cell lines and patient tumor tissues including triple negative breast cancer (TNBC) cell lines and patient samples, making AXL a potent novel target for cancer therapy, specifically for TNBC treatment. We also engineered T cells with a CAR consisting of a novel single-chain variable fragment against AXL and revealed its antigen-specific cytotoxicity and ability to release cytokines in a TNBC cell line and other AXL-positive tumors in vitro. Furthermore, AXL-CAR-T cells displayed a significant anti-tumor effect and in vivo persistence in a TNBC xenograft model. Taken together, our findings indicate that AXL-CAR-T cells can represent a promising therapeutic strategy against TNBC.

• 出版日期2018-9
• 单位第四军医大学; 吉林大学; 北京中医药大学; 中国人民解放军空军军医大学