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.

中文翻译：

---

抗EGFR变体III CAR-T细胞疗法和PD-1检查点阻滞对小鼠胶质母细胞瘤的联合抗肿瘤作用。

胶质母细胞瘤是最致命的癌症之一。很大程度上由于免疫抑制性肿瘤微环境，例如PD-1介导的T细胞衰竭，对实体瘤的嵌合抗原受体（CAR）-T细胞疗法远未令人满意。在本研究中，我们研究了抗EGFR变体III CAR-T细胞疗法和PD-1检查点阻断对胶质母细胞瘤在小鼠模型中的联合抗肿瘤作用。结果表明，具有PD-1阻滞作用的CAR-T细胞在体外具有更高的杀伤效率。此外，具有PD-1阻滞作用的CAR-T细胞对胶质母细胞瘤显示出更有效和持久的治疗效果，并导致小鼠模型中的肿瘤浸润淋巴细胞（TIL）数量显着增加。结论，通过克服TIL的衰竭，PD-1检查点的阻断显着增强了抗人EGFRvIII CAR-T细胞的抗肿瘤活性。本研究的结果为提高实体瘤中CAR-T细胞疗法的效力提供了一种新颖的策略。