Department of Medical Oncology, Chinese People's Liberation Army General Hospital, Beijing 100853, PR China; Beijing DCTY® Biotech CO., LTD, Beijing 102200, PR China.
Department of Medical Oncology, Chinese People's Liberation Army General Hospital, Beijing 100853, PR China; Beijing DCTY® Biotech CO., LTD, Beijing 102200, PR China.
Cell Immunol. 2020 Jun;352:104112. doi: 10.1016/j.cellimm.2020.104112. Epub 2020 Apr 9.
Glioblastoma is one of the deadliest cancers. Chimeric antigen receptor (CAR)-T cell therapy against solid tumors has been far from satisfactory largely due to the immunosuppressive tumor microenvironment, such as PD-1 mediated T cell exhaustion. In the present study, we investigated the combined antitumor effects of anti-EGFR variant III CAR-T cell therapy and PD-1 checkpoint blockade on glioblastoma in mouse model. The results demonstrated that CAR-T cells with PD-1 blockade exhibit higher killing efficiency in vitro. Additionally, CAR-T cells with PD-1 blockade showed more effective and persistent therapeutic effects on glioblastoma and led to significantly increased number of tumor infiltrating lymphocytes (TILs) in the mouse model. In conclusion, PD-1 checkpoint blockade significantly enhanced the antitumor activity of anti-human EGFRvIII CAR-T cells by overcoming TILs exhaustion. The outcomes of the present study provide a novel strategy for improving the potency of CAR-T cell therapies in solid tumors.
胶质母细胞瘤是最致命的癌症之一。嵌合抗原受体（CAR）-T 细胞疗法治疗实体瘤的效果远不理想，主要原因是肿瘤微环境具有免疫抑制性，例如 PD-1 介导的 T 细胞耗竭。在本研究中，我们研究了抗 EGFR 变异 III 型 CAR-T 细胞治疗联合 PD-1 检查点阻断对小鼠模型中胶质母细胞瘤的联合抗肿瘤作用。结果表明，PD-1 阻断的 CAR-T 细胞在体外具有更高的杀伤效率。此外，PD-1 阻断的 CAR-T 细胞对胶质母细胞瘤具有更有效和持久的治疗作用，并导致小鼠模型中肿瘤浸润淋巴细胞（TIL）的数量显著增加。总之，PD-1 检查点阻断通过克服 TIL 耗竭显著增强了抗人 EGFRvIII CAR-T 细胞的抗肿瘤活性。本研究的结果为提高 CAR-T 细胞疗法在实体瘤中的疗效提供了一种新策略。
