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

被引:23
作者
Wu, Di [1 ]
Wang, Jing [2 ]
Cai, Yunlang [2 ]
Ren, Mulan [2 ]
Zhang, Yuxia [1 ,2 ]
Shi, Fangfang [1 ,3 ]
Zhao, Fengshu [1 ]
He, Xiangfeng [4 ]
Pan, Meng [1 ]
Yan, Chunguang [1 ]
Dou, Jun [1 ]
机构
[1] Southeast Univ, Sch Med, Dept Pathogen Biol & Immunol, Nanjing 210009, Jiangsu, Peoples R China
[2] Southeast Univ, Sch Med, Zhongda Hosp, Dept Gynecol & Obstet, Nanjing 210009, Jiangsu, Peoples R China
[3] Southeast Univ, Zhongda Hosp, Dept Oncol, Nanjing 210009, Jiangsu, Peoples R China
[4] Nantong Univ, Affiliated Tumor Hosp, Dept Med Oncol, Nantong 226361, Peoples R China
基金
中国国家自然科学基金;
关键词
Epithelial ovarian cancer; Cancer stem cells; Vaccine; Antitumor immunity; MESENCHYMAL TRANSITION; TUMOR VACCINE; METASTASIS; EXPRESSION; ALDH1; RESISTANCE; EFFICACY; THERAPY; CD44;
D O I
10.1186/s13048-015-0196-5
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
pn 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-gamma, decreased TGF-beta 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(+)D44(+)CSC-based vaccine may induce the anti-ovarian cancer immunity against tumor growth by reducing the CD117(+)CD44(+)CSC population.
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页数:10
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