EGLIF-CAR-T cells secreting PD-1 blocking antibodies significantly mediate the elimination of gastric cancer

Abstract

Objective: To 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. Methods: Second-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. Results: EGFR-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. Conclusion: EGFR-CAR-T cells secreting PD-1 scFv are highly effective against gastric cancer and offer new insights into anti-cancer immunotherapy.