Combined antitumor effects of anti-EGFR variant III CAR-T cell therapy and PD-1 checkpoint blockade on glioblastoma in mouse model

Abstract

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.

Keywords: Chimeric antigen receptor; EGFR variant III; Glioblastoma; Programmed death-1; Programmed death-ligand 1.