1 Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China.
2 Department of Gastroenterology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
Hum Gene Ther. 2019 Apr;30(4):402-412. doi: 10.1089/hum.2018.229. Epub 2019 Mar 13.
Chimeric antigen receptor-modified T cells (CAR-T cells) have emerged as a promising cancer immunotherapy for solid tumors. Epithelial cell adhesion molecule (EpCAM) is overexpressed in a variety of tumors and is recognized as a biomarker for circulating tumor cells and cancer stem cells, representing an attractive target for adoptive T-cell immunotherapy. This study generated third-generation CAR-T cells with redirected specificity to EpCAM (EpCAM CAR-T) by lentiviral vector. The study demonstrated that EpCAM CAR-T cells can elicit lytic cytotoxicity to target cells in an EpCAM-dependent manner and secrete cytotoxic cytokines, including interferon gamma and tumor necrosis factor alpha. Furthermore, adoptive transfer of EpCAM CAR-T cells significantly delayed tumor growth and formation in xenograft models. In addition, the safety evaluation showed that CAR-T cells have no systemic toxicity in mice. The data confirmed the antitumor ability and safety of CAR-T cells targeting EpCAM and may provide a new target for CAR-T cell therapies in treating solid tumors.
嵌合抗原受体修饰的 T 细胞（CAR-T 细胞）已成为实体瘤治疗的一种很有前途的癌症免疫疗法。上皮细胞黏附分子（EpCAM）在多种肿瘤中过度表达，被认为是循环肿瘤细胞和癌症干细胞的生物标志物，是过继性 T 细胞免疫治疗的一个有吸引力的靶点。本研究通过慢病毒载体生成了第三代针对 EpCAM 的重定向特异性 CAR-T 细胞（EpCAM CAR-T）。研究表明，EpCAM CAR-T 细胞能够以 EpCAM 依赖的方式对靶细胞产生裂解细胞毒性，并分泌细胞毒性细胞因子，包括干扰素 γ 和肿瘤坏死因子 α。此外，EpCAM CAR-T 细胞的过继转移显著延迟了异种移植模型中的肿瘤生长和形成。此外，安全性评估表明，CAR-T 细胞在小鼠中没有全身毒性。这些数据证实了针对 EpCAM 的 CAR-T 细胞的抗肿瘤能力和安全性，可能为 CAR-T 细胞治疗实体瘤提供了新的靶点。
