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


CONCLUSIONS
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.
Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, 210009, China.
Di
D
Wu
Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
Jing
J
Wang
Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China. ylseu63@sohu.com.
Yunlang
Y
Cai
Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
Mulan
M
Ren
Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, 210009, China.|Department of Gynecology & Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
Yuxia
Y
Zhang
Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, 210009, China.|Department of oncology, Zhongda Hospital, Southeast University, Nanjing, 210009, China.
Fangfang
F
Shi
Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, 210009, China.
Fengshu
F
Zhao
Department of Medical Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, 226361, China.
Xiangfeng
X
He
Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, 210009, China.
Meng
M
Pan
Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, 210009, China.
Chunguang
C
Yan
Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing, 210009, China. njdoujun@seu.edu.cn.
Jun
J
Dou
D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D000917:Antibody Formation; D019496:Cancer Vaccines / Q000494:pharmacology*; D000077216:Carcinoma, Ovarian Epithelial; D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D007527:Isoenzymes / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D014411:Neoplastic Stem Cells / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology; D050697:Retinal Dehydrogenase / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014611:Vaccination
D019496:Cancer Vaccines; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase; D019009:Proto-Oncogene Proteins c-kit