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.