Format

Send to

Choose Destination
Vaccine. 2008 Oct 29;26(46):5855-63. doi: 10.1016/j.vaccine.2008.08.027. Epub 2008 Sep 2.

alpha-Galactosylceramide enhances the protective and therapeutic effects of tumor cell based vaccines for ovarian tumors.

Author information

1
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.

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.

PMID:
18771701
PMCID:
PMC2597163
DOI:
10.1016/j.vaccine.2008.08.027
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center