Vaccination with embryonic stem cells generates effective antitumor immunity against ovarian cancer
Author(s) -
Zujuan Zhang,
Xinhua Chen,
Xiao-Hong Chang,
Xue Ye,
Yi Li,
Heng Cui
Publication year - 2012
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2012.1195
Subject(s) - embryonic stem cell , biology , ovarian cancer , immune system , vaccination , immunology , immunogenicity , stem cell , cancer , immunity , cancer research , andrology , medicine , microbiology and biotechnology , biochemistry , genetics , gene
To date, only a few studies have suggested that human embryonic stem cells(hESCs) might effectively immunize against colon and lung cancer. The purposeof this study was to investigate the therapeutic potential of hESCs as a vaccineto induce widespread antitumor effects in different animal models and varioustypes of cancer. C57BL/6 mice with ID8 ovarian cancer cell and Fischer 344 ratswith NuTu-19 ovarian cancer cell models were used. Fifty-four mice were dividedinto six groups with nine mice in each group. Each mouse was immunized with pre-inactivatedhESCs (H9) or mouse embryonic stem cells (mESCs; IVP-ES1) or ID8 or phosphate-bufferedsaline (PBS). Twenty-four rats were divided into four groups with six rats ineach group, each rat immunized with pre-inactivated hESCs (H9) or NuTu-19 or PBS.After the vaccination, each mouse was challenged with live ID8 cells subcutaneously,and each rat was challenged with live NuTu-19 cells intraperitoneally. We discoveredthat vaccination of mice with the hESC line H9 and the mESC line IVP-ES1 generatedconsistent cellular and humoral immune responses against ID8 ovarian cancer. H9and IVP-ES1 vaccinated mice obtained antitumor immune protection, and H9 vaccinatedrats had the longest survival time and least distant metastases. No evidence ofside-effects was observed. We also compared the immunogenicity against ovariancancer between the hESC line, H9, and the mESC line, IVP-ES1, that derived fromthe inner cell mass in different species. We found that there were no significantdifferences between them. Furthermore, immunohistochemical staining revealed thatseveral oncogenes and tumor suppressor genes, such as HER-2, C-myc, p53, and nm23,were expressed in H9, many of which were also shared by ovarian cancer. hESC vaccinescan induce antitumor effects in two animal models and in ovarian cancer, indicatingthat the activity of the vaccine is universal, and, more importantly, it is safe.
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