EGFR-CAR-T cells secreting PD-1 antibody significantly suppress the progression of gastric cancer / 中国肿瘤生物治疗杂志
Chinese Journal of Cancer Biotherapy
;
(6): 1336-1344, 2020.
Artigo
em Chinês
| WPRIM
| ID: wpr-862240
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Idioma:
Chinês
Revista:
Chinese Journal of Cancer Biotherapy
Ano de publicação:
2020
Tipo de documento:
Artigo
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