2005 Fiscal Year Final Research Report Summary
The development of immuno-modulation therapy by use of ES cell-derived dendritic cells
| Project/Area Number |
16590988
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Kumamoto University |
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Principal Investigator |
SENJU Satoru KUMAMOTO UNIV., GRAD.SCHL.MED.SCIENCES, ASSOCIATE PROFESSOR, 大学院・医学薬学研究部, 助教授 (50274709)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Yasuharu KUMAMOTO UNIV., GRAD.SCHL.MED.SCIENCES, PROFESSOR, 大学院・医学薬学研究部, 教授 (10156119)
IRIE Atsushi KUMAMOTO UNIV., GRAD.SCHL.MED.SCIENCES, ASSOCIATE, 大学院・医学薬学研究部, 助手 (30250343)
NAKATSURA Tetsuya KUMAMOTO UNIV., GRAD.SCHL.MED.SCIENCES, ASSOCIATE, 大学院・医学薬学研究部, 助手 (30343354)
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| Project Period (FY) |
2004 – 2005
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| Keywords | ES cells / dendritic cells / immunity / anti-tumor immunotherapy / chemokine / autoimmune disease / MHC |
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| Research Abstract |
In the previous study, we developed a method to generate dendritic cells (DC) from mouse embryonic stem (ES) cells (ES-DC). Genetic modification of ES-DC can readily be done by transfection of ES cells and subsequent their differentiation to DC. In this research period, we carried out the following projects.
Anti-tumor immunotherapy by ES-DC
Immunization with DC expressing antigen plus T cell-attracting chemokines provided protection from antigen-expressing tumor cells more potently than that with antigen only. We demonstrated that anti-tumor immunotherapy with ES-DC was effective even in the allogeneic recipient mice, if some of MHC alleles were shared by the ES-DC and the mice. ES-DC expressing Glypican-3, a recently identified oncofetal antigen, induced protective immunity against highly metastatic mouse melanoma, B16-F10.
Antigen-specific down-modulation of immune response by ES-DC
We tried to establish a method for antigen-specific down-modulation of immune response by ES-DC expressing antigen along with immuno-suppressive molecules. We demonstrated that severity of myelin oligodendrocyte glycoprotein (MOG) peptide-induced experimental autoimmune encephalomyelitis (EAE) was reduced in mice treated with the double-transfectant ES-DC, presenting myelin oligodendrocyte glycoprotein (MOG) peptide in the context of MHC class II molecules and simultaneously expressing TNF-related apoptosis-inducing ligand (TRAIL) or Programmed Death-1 ligand (PD-L1). In addition, we obtained several lines of evidence showing that regulatory T cells were involved in the disease-preventive effect induced by ES-DC expressing TRAIL.
Generation of ES-DC form primate ES cells
For future clinical applications of this technology, it is necessary to develop a method to generate DC from human ES cells. Before we use human ES cells, we established a method to generate ES-DC from a cynomolgus monkey ES cell line, which is similar in many aspects to human ES cells.
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[Journal Article] Embryonic stem cell-derived dendritic cells expressing Glypican-3, a recently identified oncofetal antigen, induce protective immunity against highly metastatic mouse melanoma, B16-F10.2006
Author(s)
Motomura, Y., Senju, S., Nakatsura, T., Matsuyoshi, H., Hirata, S., Monji, M., Komori, H., Fukuma, D., Baba, H., Nishimura, Y.
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Journal Title
Cancer Research 66
Pages: 2414-2422
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Prevention of experimental autoimmune encephalomyelitis by transfer of ES cell-derived dendritic cells expressing MOG peptide along with TRAIL or PD-L1.2005
Author(s)
Hirata, S., Senju, S., Matsuyoshi, H., Fukuma, D., Uemura, Y., Nishimura, Y.
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Journal Title
J.Immunol. 174
Pages: 1888-1897
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cancer prevention with semi-allogeneic ES cell-derived dendritic cells.2005
Author(s)
Fukuma, D., Matsuyoshi, H., Hirata, S., Kurisaki, A., Yoshitake, Y., Sinohara, M., Nishimura, Y., Senju, S.
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Journal Title
Biochem.Biophys.Res.Comm. 335
Pages: 5-13
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] DNA vaccination of HSP105 leads to tumor rejection of colorectal cancer and melanoma in mice through activation of both CD4^+T cells and CD8^+ T cells.2005
Author(s)
Miyazaki, M.^*, Nakatsura, T.^*, Senju, S., Monji, M., Hosaka, S., Komori, H., Yoshitake, Y., Motomura, Y., Yokomine, K., Minohara, M., Kubo, T., Ishihara, K., Hatayama, T., Ogawa, M., Nishimura, Y.(^*equal contribution)
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Journal Title
Cancer Science 96
Pages: 695-705
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Therapeutic effect of a-galactosylceramide-loaded dendritic cells genetically engineered to express SLC/CCL21 along with tumor antigen against peritoneally disseminated tumor cells.2005
Author(s)
Matsuyoshi, H., Hirata, S., Yoshitake, Y., Motomura, Y., Fukuma, D., Kurisaki, A., Nakatsura, T., Nishimura, Y., Senju, S.
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Journal Title
Cancer Science 96
Pages: 889-896
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Direct recognition and lysis of leukemia cells by WT1-specific CD4^+T lymphocytes in an HLA class II-restricted manner.2005
Author(s)
Guo, Y., Niiya, H., Azuma, T., Uchida, N., Yakushijin Y., Sakai, I., Hato, T., Takahashi, M., Senju, S., Nishimura, Y., Yasukawa M.
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Journal Title
Blood 106
Pages: 1415-1418
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Mouse homologue of a novel human oncofetal antigen, Glypican-3, evokes T cell-mediated tumor rejection without autoimmune reactions in mice.2004
Author(s)
Nakatsura, T., Komori, H., Kubo, T., Yoshitake, Y., Senju, S., Katagiri, T., Furukawa, Y., Oagawa, M., Nakamura, Y., Nishimura, Y.
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Journal Title
Clin.Cancer Res 10
Pages: 8630-8640
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification of glypican-3 as a novel tumor marker for melanoma.2004
Author(s)
Nakatsura, T., Kageshita, T., Ito, S., Wakamatsu, K., Monji, M., Ikuta, Y., Senju, S., Ono, T., Nishimura, Y.
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Journal Title
Clin.Cancer Res. 10
Pages: 6612-6621
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Proliferation potential-related protein, an ideal esophageal cancer antigen for immnotherapy, identified using complementary DNA microarray analysis.2004
Author(s)
Yoshitake, Y., Nakatsura, T., Monji, M., Senju, S., Matsuyoshi, H., Tsukamoto, H., Hosaka, S., Komori, H., Fukuma, D., Ikuta, Y., Katagiri, T., Furukawa, Y., Ito, H., Shinohara, M., Nakamura, Y., Nishimura, Y.
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Journal Title
Clin.Cancer Res. 10
Pages: 6437-6448
Description
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[Journal Article] Identification of a novel human cancer/testis antigen, KM-HN-1, recognized by cellular and humeral immune responses.2004
Author(s)
Monji, M., Nakatsura, T., Senju, S., Yoshitake, Y., Sawatsubashi, M., Shinohara, M., Kageshita, T., Ono, T., Inokuchi, A., Nishimura, Y.
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Journal Title
Clin.Cancer Res. 10
Pages: 6047-6057
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Detection of the novel autoantibody (anti-UACA antibody) in patients with Graves disease.2004
Author(s)
Ohkura, T., Taniguchi, S., Yamada, K., Nishio, N., Okamura, T., Yoshida, A., Kamijou, K., Fukata, S., Kuma, K., Inoue, Y., Hisatome, I., Senju, S., Nishimura Y., Shigemasa, C.
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Journal Title
Biochem.Biophys.Res.Comm. 321
Pages: 432-440
Description
「研究成果報告書概要(欧文)」より
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