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The development of immuno-modulation therapy by use of ES cell-derived dendritic cells

Research Project

Project/Area Number 16590988
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionKumamoto University

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)

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)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsES cells / dendritic cells / immunity / anti-tumor immunotherapy / chemokine / autoimmune disease / MHC / 胚性幹細胞 / 免疫応答 / 免疫寛容 / 再生医療 / 臓器移植 / MHC / 遺伝子導入 / 実験的自己免疫性脳脊髄炎 / 免疫制御性T細胞 / T細胞
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.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (48 results)

All 2006 2005 2004

All Journal Article (46 results) Patent(Industrial Property Rights) (2 results)

  • [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.et al.
    • Journal Title

      Cancer Research 66

      Pages: 2414-2422

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.
    • Journal Title

      Cancer Research 66

      Pages: 2414-2422

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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. et al.
    • Journal Title

      Cancer Research 66

      Pages: 2414-2422

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prevention of experimental autoimmune encephalomyelitis by transfer of ES cell-derived dendritic cells expressing MOG peptide along with TRAIL or PD-LI.2005

    • Author(s)
      Hirata, S. et al.
    • Journal Title

      J. Immunol. 174

      Pages: 1888-1897

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cancer prevention with semi-allogeneic ES cell-derived dendritic cells.2005

    • Author(s)
      Fukuma, D. et al.
    • Journal Title

      Biochem. Biophys. Res. Comm. 335

      Pages: 5-13

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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. et al.
    • Journal Title

      Cancer Science 96

      Pages: 695-705

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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. et al.
    • Journal Title

      Cancer Science 96

      Pages: 889-896

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [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.et al.
    • Journal Title

      Blood 106

      Pages: 1415-1418

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 樹状細胞の移入による免疫抑制療法2005

    • Author(s)
      平田真哉, 千住 覚, 西村泰治
    • Journal Title

      臨床免疫 43(5)

      Pages: 603-607

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 抗原提示細胞をターゲットとした免疫抑制法2005

    • Author(s)
      平田真哉, 千住 覚, 西村泰治
    • Journal Title

      分子リウマチ 2(1)

      Pages: 47-54

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] HLA不適合と拒絶反応2005

    • Author(s)
      松吉秀武, 千住 覚, 門司幹男, 西村泰治
    • Journal Title

      臨床免疫学(上) 63(4)

      Pages: 621-631

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [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.
    • Journal Title

      J.Immunol. 174

      Pages: 1888-1897

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.
    • Journal Title

      Biochem.Biophys.Res.Comm. 335

      Pages: 5-13

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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)
    • Journal Title

      Cancer Science 96

      Pages: 695-705

    • NAID

      10017091223

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.
    • Journal Title

      Cancer Science 96

      Pages: 889-896

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.
    • Journal Title

      Blood 106

      Pages: 1415-1418

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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. et al.
    • Journal Title

      J.Immunol. 174

      Pages: 1888-1897

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Anti-cancer immunotherapy with semi-allogeneic embryonic stem cell-derived dendritic cells genetically engineered to express a model tumor antigen.2005

    • Author(s)
      Fukuma, D. et al.
    • Journal Title

      Biochem.Biophys.Res.Comm. 335

      Pages: 5-13

    • Related Report
      2005 Annual Research Report
  • [Journal Article] DNA vaccination of HSP105 leads to tumor rejection of colorectal cancer and melanoma in mice through activation of both CD4^+ and CD8^+ T cells.2005

    • Author(s)
      Miyazaki, M. et al.
    • Journal Title

      Cancer Science 96

      Pages: 695-705

    • Related Report
      2005 Annual Research Report
  • [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.et al.
    • Journal Title

      Blood 106

      Pages: 1415-1418

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 樹状細胞の移入による免疫抑制療法2005

    • Author(s)
      平田真哉, 千住覚, 西村泰治
    • Journal Title

      臨床免疫 43(5)

      Pages: 603-607

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 抗原提示細胞をターゲットとした免疫抑制法2005

    • Author(s)
      平田真哉, 千住覚, 西村泰治
    • Journal Title

      分子リウマチ 2(1)

      Pages: 47-54

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Prevention of experimental autoimmune encephalomyelitis by transfer of EScell-derived dendritic cells expressing MOG peptide along with TRAIL or PD-1.2005

    • Author(s)
      Hirata, S.et al.
    • Journal Title

      J.Immunol. 174

      Pages: 1888-1897

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 抗原提示細胞をターゲットとした免疫抑制療法2005

    • Author(s)
      平田真哉, 千住覚, 西村泰治
    • Journal Title

      分子リウマチ 2・1

      Pages: 47-54

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Mouse homologue of a nobel human oncofetal antigen, Glypican-3, evokes T cell-mediated tumor rejection without autoimmune reactions in mice.2004

    • Author(s)
      Nakatsura, T. et al.
    • Journal Title

      Clin. Cancer Res 10

      Pages: 8630-8640

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification of glypican-3 as a novel tumor marker for melanoma.2004

    • Author(s)
      Nakatsura, T. et al.
    • Journal Title

      Clin. Cancer Res 10

      Pages: 6612-6621

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Proliferation potential-related protein, an ideal esophageal cancer antigen for immnotherapy, identified using complementary DNA microarray analysis.2004

    • Author(s)
      Yoshitake, Y. et al.
    • Journal Title

      Clin. Cancer Res. 10

      Pages: 6437-6448

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification of a novel human cancer/testis antigen, KM-HN-1, recognized by cellular and humoral immune responses.2004

    • Author(s)
      Monji, M. et al.
    • Journal Title

      Clin. Cancer Res. 10

      Pages: 6047-6057

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Detection of the novel autoantibody (anti-UACA antibody) in patients with Graves disease.2004

    • Author(s)
      Ohkura, T. et al.
    • Journal Title

      Biochem. Biophys. Res. Comm. 321

      Pages: 432-440

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 抗原とケモカインを共発現させたES細胞由来の樹状細胞を用いた抗腫瘍免疫療法2004

    • Author(s)
      松吉秀武, 千住 覚, 西村泰治
    • Journal Title

      臨床免疫 42(1)

      Pages: 110-114

    • NAID

      80016807917

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ES細胞由来の樹状細胞による免疫制御2004

    • Author(s)
      松吉秀武, 千住 覚, 西村泰治
    • Journal Title

      感染、炎症、免疫-連載 : ビジュアルデビュー 34(2)

      Pages: 32-39

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 抗原提示細胞をターゲットとした免疫抑制法2004

    • Author(s)
      平田真哉, 千住 覚, 西村泰治
    • Journal Title

      Mebio 21(10)

      Pages: 33-41

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.
    • Journal Title

      Clin.Cancer Res 10

      Pages: 8630-8640

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.
    • Journal Title

      Clin.Cancer Res. 10

      Pages: 6612-6621

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.
    • Journal Title

      Clin.Cancer Res. 10

      Pages: 6437-6448

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.
    • Journal Title

      Clin.Cancer Res. 10

      Pages: 6047-6057

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.
    • Journal Title

      Biochem.Biophys.Res.Comm. 321

      Pages: 432-440

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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.et al.
    • Journal Title

      Clin.Cancer Res. 10

      Pages: 8630-8640

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of glypican-3 as a novel tumor marker for melanoma.2004

    • Author(s)
      Nakatsura, T.et al.
    • Journal Title

      Clin.Cancer Res. 10

      Pages: 6612-6621

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Proliferation potential-related protein, an ideal esophageal cancer antigen forimmnotherapy, identified using complementary DNA microarray analysis.2004

    • Author(s)
      Yoshitake, Y.et al.
    • Journal Title

      Clin.Cancer Res. 10

      Pages: 6437-6448

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Identification of a novel human cancer/testis antigen, KM-HN-1, recognized by cellular and humoral immune responses.2004

    • Author(s)
      Monji, M.et al.
    • Journal Title

      Clin.Cancer Res. 10

      Pages: 6047-6057

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Detection of the novel autoantibody (anti-UACA antibody) in patients with Graves disease.2004

    • Author(s)
      Ohkura, T.et al.
    • Journal Title

      Biochem.Biophys.Res.Comm. 321

      Pages: 432-440

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Enhanced priming of antigen-specific CTL in vivo by transfer of ES cell-derived dendritic cells expressing chemokine along with antigenic protein ; application to anti-tumor vaccination.2004

    • Author(s)
      Matsuyoshi, H.et al.
    • Journal Title

      J.Immunol. 172

      Pages: 776-786

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ES細胞由来の樹状細胞による免疫制御2004

    • Author(s)
      松吉秀武, 千住 覚, 西村泰治
    • Journal Title

      感染、炎症、免疫-連載:ビジュアルデビュー 34・2

      Pages: 32-39

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 抗原とケモカインを共発現させたES細胞由来の樹状細胞を用いた抗腫瘍免疫療法2004

    • Author(s)
      松吉秀武, 千住 覚, 西村泰治
    • Journal Title

      臨床免疫 42・1

      Pages: 110-114

    • NAID

      80016807917

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 抗原提示細胞をターゲットとした免疫抑制法2004

    • Author(s)
      平田真哉, 千住覚, 西村泰治
    • Journal Title

      Mebio 21・10

      Pages: 33-41

    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 霊長類動胚性幹細胞から樹状細胞の製造方法2004

    • Inventor(s)
      千住覚, 西村泰治
    • Industrial Property Rights Holder
      千住覚, 田辺製薬株式会社
    • Industrial Property Number
      2004-249062
    • Filing Date
      2004-08-27
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 霊長類動物胚性幹細胞から樹状細胞の製造方法2004

    • Inventor(s)
      千住 覚, 西村 泰治
    • Industrial Property Rights Holder
      千住 覚, 田辺製薬株式会社
    • Filing Date
      2004-08-27
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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