Antitumor activity of chimeric antigen receptor NK-92 cells targeting PSCA anainst cervical cancer
DOI:10.3872/j.issn.1007-385X.2020.12.005
- VernacularTitle:靶向PSCA的CAR-NK-92细胞对宫颈癌的抗瘤作用
- Author:
MA Huan
1
;
ZHANG Xianyu
1
;
ZHANG Fei
1
;
LI Jinqiu
1
;
LU Xiurong
1
;
YUAN Na
1
;
HAO Xiaohui
1
;
ZHANG Zhilin
1
Author Information
1. Department of Radiotherapy, the First Affiliated Hospital of Hebei North University, Shijiazhuang 075000, Hebei, China
- Publication Type:Journal Article
- Keywords:
prostate stem cell antigen (PSCA);
cervical cancer;
NK-92 cell;
transplanted tumor in nude mice;
immunotherapy
- From:
Chinese Journal of Cancer Biotherapy
2020;27(12):1345-1350
- CountryChina
- Language:Chinese
-
Abstract:
[Abstract] Objective: To construct and verify the anti-tumor activity of chimeric antigen receptor (CAR) modified NK-92 cells (CAR-NK-92 cells) targeting prostate stem cell antigen (PSCA) in cervical cancer. Methods: Lentiviral vector expressing CAR targeting PSCA was constructed, and PSCA CAR-NK-92 cells were obtained by lentivirus transfection. The expression of PSCA in human cervical cancer cells was determined by Flow cytometry and Western blotting. The killing effect of PSCA CAR-NK-92 cells against cervical cancer cells was verified by co-incubation of effector and target cells in vitro, and the tumor inhibitory ability of PSCA CAR-NK-92 cells was verified with the nude mice xenograft model in vivo. Results: PSCA CAR-NK-92 cells were successfully constructed. PSCA was highly expressed in human cervical cancer Hela and MS751 cells (all P<0.01). In vitro co-incubation results showed that PSCA CAR-NK-92 cells could lyse PSCA+ cervical cancer transplanted tumor in a dose-dependent manner. In vivo anti-tumor data showed that PSCA CAR-NK-92 cells significantly inhibited the growth of cervical cancer cells compared with NK-92 cells transfected with vehicle vectors (P<0.01). In addition, PSCA CAR-NK-92 cells could effectively infiltrate tumor tissues and promote the secretion of anti-tumor cytokines TNF-α and IFN-γ (all P<0.01). Conclusion: The CAR-NK-92 targeting PSCA shows good anti-tumor effect on PSCA+ tumor cells both in vitro and in vivo, and has potential to be a therapeutic strategy for cervical cancer.
- Full text:20201205.pdf