Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
Pathology Department Weifang Heart Hospital, Shandong Province, PR China.
Cell Immunol. 2018 Sep;331:49-58. doi: 10.1016/j.cellimm.2018.05.004. Epub 2018 May 14.
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.
鉴定嵌合抗原受体修饰的 T 淋巴细胞（CAR-T）治疗实体瘤的靶点是一个亟待解决的问题。在这项研究中，我们首次表明受体酪氨酸激酶 AXL 在各种肿瘤细胞系和包括三阴性乳腺癌（TNBC）细胞系和患者样本在内的患者肿瘤组织中过表达，使 AXL 成为癌症治疗的一个强有力的新靶点，特别是用于 TNBC 的治疗。我们还构建了一种 CAR-T 细胞，该细胞含有针对 AXL 的新型单链可变片段，并在体外的 TNBC 细胞系和其他 AXL 阳性肿瘤中揭示了其抗原特异性细胞毒性和细胞因子释放能力。此外，AXL-CAR-T 细胞在 TNBC 异种移植模型中表现出显著的抗肿瘤作用和体内持久性。综上所述，我们的研究结果表明，AXL-CAR-T 细胞可能成为治疗 TNBC 的一种很有前途的治疗策略。
