Cancer Management and Research (Sep 2020)
EGLIF-CAR-T Cells Secreting PD-1 Blocking Antibodies Significantly Mediate the Elimination of Gastric Cancer
Abstract
Jing-Tao Zhou,1,* Jiang-Hao Liu,2,* Ting-Ting Song,2 Bo Ma,3 Nuermaimait Amidula,1 Chao Bai4 1General Surgery, The Seventh Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2General Surgery, Xinjiang Uygur Autonomous Region Eighth People’s Hospital, Urumqi, People’s Republic of China; 3General Surgery, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 4Department of Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao BaiDepartment of Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, No. 137 South Liyushan Road, New District, Urumqi 830000, People’s Republic of ChinaTel +86 991-4364657Email [email protected]: 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.Keywords: EGLIF-CAR-T cells, PD-1 blocking antibodies, elimination, gastric cancer
