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

Jing-Tao Zhou; Jiang-Hao Liu; Ting-Ting Song; Bo Ma; Nuermaimait Amidula; Chao Bai

doi:10.2147/CMAR.S260915

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

Cancer Manag Res. 2020 Sep 23:12:8893-8902. doi: 10.2147/CMAR.S260915. eCollection 2020.

Authors

Jing-Tao Zhou^#¹, Jiang-Hao Liu^#², Ting-Ting Song², Bo Ma³, Nuermaimait Amidula¹, Chao Bai⁴

Affiliations

¹ General Surgery, The Seventh Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China.
² General Surgery, Xinjiang Uygur Autonomous Region Eighth People's Hospital, Urumqi, People's Republic of China.
³ General Surgery, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China.
⁴ Department of Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, People's Republic of China.

^# Contributed equally.

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.

Keywords: EGLIF-CAR-T cells; PD-1 blocking antibodies; elimination; gastric cancer.

Grants and funding

This work is supported by Autonomous Region Health and Family Planning Commission’s special scientific research project for young medical science and technology talents (WJWY-202006 and WJWJ-201817).