title: Study on the mesothelin-specific cytotoxicity against epithelial ovarian cancer with full-length mesothelin cDNA-transduced dendritic cells.
abstract: Epithelial ovarian cancer (EOC) has the highest mortality rate among the various types of gynecological cancers. As the current therapeutic approaches are not enough, the development of more effective treatments to improve the survival of patients with EOC is urgently needed. Mesothelin (MSLN) is a cell surface glycoprotein, which is overexpressed in ovarian cancer tissues. As an immunotherapeutic approach, in this study, we investigated whether the genetically modified dendritic cells (DCs) expressing MSLN could induce cytotoxic T lymphocytes (CTLs) to produce MSLN-specific cytotoxic activity against EOCs. Here, we report that DCs transfected with full-length coding sequence of MSLN could induce MSLN-specific CTLs responses against ovarian cancer lines SKOV3 and OVCAR3 in vitro. Additionally, we identified that the death rates of ovarian cancer cells, killed by MSLN-specific CTLs, were significantly higher than the normal CTLs. Furthermore, IFN-γ production by stimulated MSLN-specific CTLs was significantly higher than that of unstimulated CTLs. This study showed that induced CTLs by DCs with full-length MSLN cDNA have effective immune response against the ovarian cancer cells, indicating that MSLN-transfected DCs vaccine has a promising prospect for the treatment of EOC.
authors.affiliation: Teaching and Research Section of Obstetrics and Gynecology, Hebei Medical University, Shijiazhuang, 050011, China; First Department of Gynecology, Cangzhou Central Hospital, Cangzhou 061001, China, czwangdonghui@hotmail.com.
authors.forename: Dong-hui
authors.initials: DH
authors.lastname: Wang
authors.forename: Xiao-hua
authors.initials: XH
authors.lastname: Wu
authors.forename: Su-min
authors.initials: SM
authors.lastname: Qian
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Yao
mesh_terms: D017209:Apoptosis; D000077216:Carcinoma, Ovarian Epithelial; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000008:administration & dosage / Q000378:metabolism*; D015316:Genetic Therapy; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D000090204:Mesothelin; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D058851:GPI-Linked Proteins; C000715527:MSLN protein, human; D007371:Interferon-gamma; D000090204:Mesothelin