EGFR-CAR-T cells secreting PD-1 antibody significantly suppress the progression of gastric cancer
DOI：10.3872/j.issn.1007-385X.2020.12.004
- VernacularTitle:分泌PD-1抗体的EGFR-CAR-T细胞可明显抑制胃癌的进展
- Author:
HUA Haiqin1
1
;
ZHENG Xiaomei1
1
;
WU Daping1
1
;
LI Fei2
2
;
REN Qing1
1
Author Information
1. Department of Oncology, Danzhou People's Hospital, Danzhou 571700, Hainan, China
2. School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Jiangsu Key Laboratory of Oncology and Intervention, Nanjing 210009, Jiangsu, China
- Publication Type:Journal Article
- Keywords:
Chimeric antigen receptor T cells;
solid tumors;
tumor immunotherapy;
PD-1
- From:
Chinese Journal of Cancer Biotherapy
2020;27(12):1336-1344
- CountryChina
- Language:Chinese
-
Abstract:
[Abstract] Objective:To explore the anti-tumor effect of CAR-T cells secreting PD-1 scFv on gastric cancer. Method: We selected EGFR as the target of CAR-T cells and constructed second-generation EGFR-CAR-T cells (EGFR BB-z) and fourth-generation EGFR-CAR-T cells secreting PD-1 scFv (EGFR BB-z/E30). The anti-tumor activity was examined after in vitro activation and long-term stimulation, and its tumor suppression ability was validated through a mouse gastric cell xenograft model. Results: EGFR was highly expressed in gastric cancer tissues and cells (all P<0.01). EGFR BB-z and EGFR BB-z/E30 cells were successfully obtained by lentivirus infection. In vitro experiments showed that compared with EGFR BB-Z, EGFR BB-Z/E30 had longer long-term proliferation ability and stronger tumor killing activity (all P<0.01). In vivo experiments also validated that EGFR BB-z/E30 had obvious tumor inhibitory function in subcutaneous gastric tumor cell transplanted xenograft model and patient-derived tumor xenograft model (PDX) (all P<0.01). It also significantly increased T cell infiltration in tumor site and decreased the expression level of PD-1 (P<0.01 or P<0.05) on EGFR BB-z/E30 cell surface as well as the high secretion of IFN-γ (P<0.05). Conclusion: EGFR-CAR-T cell EGFR BB-z/E30 secreting PD-1 scFv can significantly inhibit the progression of gastric cancer and provide a potential new strategy for the treatment of gastric cancer.
- Full text:20201204.pdf
