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

Di Wu, Jing Wang, Yunlang Cai, Mulan Ren, Yuxia Zhang, Fangfang Shi, Fengshu Zhao, Xiangfeng He, Meng Pan, Chunguang Yan, Jun Dou

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. 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. 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. 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.