Effect of targeted ovarian cancer immunotherapy using ovarian cancer stem cell vaccine

Abstract

Background: Accumulating evidence has shown that different immunotherapies for ovarian cancer might overcome barriers to resistance to standard chemotherapy. The vaccine immunotherapy may be a useful one addition to conditional chemotherapy regimens. The present study investigated the use of vaccine of ovarian cancer stem cells (CSCs) to inhibit ovarian cancer growth. Methods: CD117+CD44+CSCs were isolated from human epithelial ovarian cancer (EOC) SKOV3 cell line by using a magnetic-activated cell sorting system. Pre-inactivated CD117+CD44+CSC vaccine was vacccinated into athymic nude mice three times, and then the mice were challenged subcutaneously with SKOV3 cells. The anti-tumor efficacy of CSC vaccine was envaluated by in vivo tumorigenicity, immune efficient analysis by flow cytometer, and enzyme-linked immunosorbent assays, respectively. Results: The CD117+ CD44+CSC vaccine increased anti-ovarian cancer efficacy in that it depressed ovarian cancer growth in the athymic nude mice. Vaccination resulted in enhanced serum IFN-γ, decreased TGF-β levels, and increased cytotoxic activity of natural killer cells in the CD117+ CD44+CSC vaccine immunized mice. Moreover, the CSC-based vaccine significantly reduced the CD117+CD44+CSC as well as the aldehyde dehydrogenase 1 positive cell populations in the ovarian cancer tissues in the xenograft mice. Conclusion: The present study provided the first evidence that human SKOV3 CD117+ CD44+CSC-based vaccine may induce the anti-ovarian cancer immunity against tumor growth by reducing the CD117+CD44+CSC population.