EGLIF-CAR-T Cells Secreting PD-1 Blocking Antibodies Significantly Mediate the Elimination of Gastric Cancer.

Abstract

ObjectiveTo investigate the anti-tumor effects of programmed cell death protein 1 (PD-1) scFv-secreting EGFR-chimeric antigen receptor-modified (CAR)-T cells against gastric cancer.MethodsSecond-generation EGFR-CAR-T cells and fourth-generation PD-1 scFv-secreting EGFR-CAR-T cells were engineered. The anti-tumor activities of chimeric antigen receptor-modified (CAR)-T cells were analyzed in vitro by long-term co-culture with gastric cancer cells. The tumor scavenging capacity in vivo was evaluated in xenograft and PDX mouse models.ResultsEGFR-CAR-T cells secreting PD-1 scFv showed enhanced long-term tumor cell killing capacity in vitro. These cells also showed significant anti-tumor effect in the subcutaneous xenograft model of gastric cancer as well as in the PDX model, and autocrine PD-1 antibody secretion significantly increased tumor infiltration of the CAR-T cells.ConclusionEGFR-CAR-T cells secreting PD-1 scFv are highly effective against gastric cancer and offer new insights into anti-cancer immunotherapy.