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Anti-mesothelin chimeric antigen receptor modified T cells for ovarian cancer



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Anti-mesothelin chimeric antigen receptor modified T cells for ovarian cancer


YANG Yongjun LI Yao YIN Li LIU Xindong BIAN Xiuwu YU Shicang

Institute of Pathology, Department of Breast Surgery, First Affiliated Hospital, Army Military Medical University (Third Military Medical University), Chongqing, 400038, China


ovarian cancer mesothelin chimeric antigen receptor modified T cells killing effect

R394.3; R73-362; R737.31

Objective    To observe the killing effect of anti-mesothelin (MSLN) chimeric antigen receptor (CAR) modified T cells (CART) for ovarian cancer cells, and explore new treatment methods and strategies for the tumor. Methods    A humanized CAR structure of anti-human MSLN was designed and ligated to a lentiviral vector. Human peripheral blood mononuclear cells were infected with associate lentivirus for introduction of CART. Western blotting, qRT-PCR and flow cytometry were used to detect the correct expression of CAR structure on the membrane surface of CART. The expression of MSLN in ovarian cancer samples and cell lines was detected by immunohistochemical assay and Western blotting. The cytotoxicity of the CART cells to kill MSLN-positive ovarian cancer cells was evaluated via in vitro and in vivo experiments. Results    Compared with normal tissues, ovarian cancer tissues highly expressed MSLN (P<0.01); The anti-MSLN-CART cells were successfully prepared, and these cells specifically recognized and killed MSLNpositive ovarian cancer cells in vitro experiments. When the E∶T ratio was 2-4∶1, the killing rate still remained at 80%. Moreover, the orthotopic xenografts of ovarian cancers in NOD/SCID mice disappeared completely after totally 1×107 MSLN-CART cells were injected via the tail vein twice. Conclusion    Anti-MSLN-CART cells can effectively, specifically and safely kill ovarian cancer cells, inhibit the growth of tumors.


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Last Update: 2018-06-13