title: alpha-Galactosylceramide enhances the protective and therapeutic effects of tumor cell based vaccines for ovarian tumors.
abstract: Ovarian cancer is one of the leading causes of death from gynecological cancers in the United States. Conventional therapies are unlikely to control advanced stage ovarian cancers, thus requiring innovative alternative therapies. In the current study, we characterized the therapeutic effect of tumor cell-based vaccines combined with the adjuvant, alpha-galactosylceramide (alpha-GalCer) using two different mouse models. Our data suggests that treatment with alpha-GalCer led to an increase in the IFN-gamma serum levels in the presence or absence of irradiated mouse ovarian surface epithelial tumor cells (MOSEC). Furthermore, administration of irradiated MOSEC tumor cells with adjuvant alpha-GalCer generated significant protective and therapeutic antitumor effects against MOSEC tumors in vaccinated C57BL/6 mice. In addition, immune cells expressing CD4, CD8 or NK1.1 markers were found to be important for the protective antitumor effects generated by irradiated tumor cell-based vaccines combined with adjuvant alpha-GalCer. We also found that treatment of a spontaneous ovarian cancer murine model, the Müllerian inhibiting substance type II receptor T antigen (TgMISIIR-TAg) transgenic mice with ovarian tumor cell-based vaccines combined with adjuvant alpha-GalCer led to prolonged survival as well as increased numbers of tumor-specific CD8+ T cells. Therefore, irradiated tumor cell-based vaccines in combination with alpha-GalCer are capable of breaking immune tolerance and generating significant antitumor effects in two different mouse tumor models. Our study serves as a foundation for future clinical translation.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Youn Seok
authors.initials: YS
authors.lastname: Choi
authors.forename: Talia
authors.initials: T
authors.lastname: Hoory
authors.forename: Archana
authors.initials: A
authors.lastname: Monie
authors.forename: Annie
authors.initials: A
authors.lastname: Wu
authors.forename: Denise
authors.initials: D
authors.lastname: Connolly
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000528:radiation effects / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000494:pharmacology*; D007371:Interferon-gamma / Q000097:blood; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation / Q000276:immunology; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000517:prevention & control*; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D016207:Cytokines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D007371:Interferon-gamma
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