The development of immune regulation by genetically modified ES-DC

• Project/Area Number: 20790693
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kumamoto University
• Principal Investigator: HIRATA Shinya Kumamoto University, 大学院・医歯学総合研究科, 助教 (60418829)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 臨床免疫学 / 移植免疫学 / ES細胞由来樹状細胞 / 糖尿病 / 制御性T細胞 / TRAIL / マウスアロ膵島移植 / マウスES細胞 / ES細胞由来の樹状細胞(ES-DC) / NODマウス / C蛋白質誘導性筋炎モデルマウス / マウスES-DC / アロ膵島移植 / 移植免疫寛容 / 抗原特異的免疫抑制 / 電気穿孔法

Research Abstract

Recent studies showed that DCs physiologically play significant roles in regulating immune responses both positively and negatively. For genetic modification of DC, we used a previously established method to generate DC from mouse ES cells in vitro (ES-DC). We tried 1) the prevention of diabetes by transfer of ES-DC expressing islet-derived antigen along with immunosuppressive molecules in NOD mice, and 2) the prolongation of islet allograft survival by transfer of ES-DC expressing immunosuppressive molecules. These strategies may also be useful for the treatment of subjects with autoimmune diseases and for the induction of transplantation tolerance.

Research Products

• [Journal Article] Pluripotent stem cells as source of dendritic cells for immune therapy. (2010)
  • Author(s): Senju, S., Hirata, S., Motomura, Y., Fukuma, D., Matsunaga, Y., Fukushima, S., Matsuyoshi, H., Nishimura, Y.
  • Journal Title: Int J Hematol 91(3) Pages: 392-400
  • NAID: 10026401004
  • Peer Reviewed
• [Journal Article] Identification of SPARC as a candidate target antigen for immunotherapy of various cancers. (2010)
  • Author(s): Inoue, M., Senju, S., Hirata, S., Ikuta, Y., Hayashida, Y., Irie, A,, Harao, M., Imai, K., Tomita, Y., Tsunoda, T., Furukawa, Y., Ito, T., Nakamura, Y., Baba, H., Nishimura, Y.
  • Journal Title: Int J Cancer (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Pluripotent stem cells as source of dendritic cells for immune therapy (2010)
  • Author(s): Senju, S., Hirata, S., et al.
  • Journal Title: Int J Hematol 91(3) Pages: 392-400
  • NAID: 10026401004
  • Peer Reviewed
• [Journal Article] Identification of SPARC as a candidate target antigen for immunotherapy of various cancers (2010)
  • Author(s): Inoue, M., Senju, S., Hirata, S., et al
  • Journal Title: Int J Cancer (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Efficient induction of human T-cell leukemia virus-l-specific CTL by chimeric particle without adjuvant as a prophylactic for adult T-cell leukemia. (2009)
  • Author(s): Kozako, T., Fukada, K., Hirata, S., White, Y., Harao, M., Nishimura, Y., Kino, Y., Soeda, S., Shimeno, H., Lemonnier, F., Sonoda, S., Arima, N.
  • Journal Title: Mol Immunol 47 Pages: 606-613
  • Peer Reviewed
• [Journal Article] An in vivo model of priming of antigen-specific human CTL by Mo-DC in NOD/Shi-scid IL2rgamma(null) (NOG) mice. (2009)
  • Author(s): Inoue, M., Senju, S., Hirata, S., Irie, A., Baba, H., Nishimura, Y.
  • Journal Title: Immunol Lett 126(1-2) Pages: 67-72
  • Peer Reviewed
• [Journal Article] Multiple Antigen-targeted Immunotherapy With alpha-Galactosylceramide-loaded and Genetically Engineered Dendritic Cells Derived From Embryonic Stem Cells. (2009)
  • Author(s): Fukushima, S., Hirata, S., Motomura, Y., Fukuma, D., Matsunaga, Y., Ikuta, Y., Ikeda, T., Kageshita, T., Ihn, H., Nishimura, Y., Senju, S.
  • Journal Title: J Immunother 32(3) Pages: 219-231
  • Peer Reviewed
• [Journal Article] (*equal contribution) Identification of the H2-Kd-restricted cytotoxic T lymphocyte epitopes of a tumor-associated antigen, SPARC, which can stimulate antitumor immunity without causing autoimmune disease in mice. (2009)
  • Author(s): Ikuta, Y. *, Hayashida, Y. *, Hirata, S., Irie, A., Senju, S., Kubo, T., Nakatsura, T., Monji, M., Sasaki, Y., Baba, H., Nishimura, Y.
  • Journal Title: Cancer Sci 100(1) Pages: 132-7
  • Peer Reviewed
• [Journal Article] TRAIL発現樹状細胞によるレギュラトリーT細胞の誘導と実験的自己免疫性脳脊髄炎の治療 (2009)
  • Author(s): 平田真哉, 千住覚, 西村泰治
  • Journal Title: 臨床-免疫・アレルギー科(科学評論社(東京)) 51(1) Pages: 72-76
  • NAID: 40016464329
• [Journal Article] Multiple Antigen-targeted Immunotherapy With alpha-Galactosylceramide-loaded and Genetically Engineered Dendritic Cells Derived From Embryonic Stem Cells (2009)
  • Author(s): Fukushima, S., Hirata, S., et al.
  • Journal Title: J Immunother 32(2) Pages: 606-613
  • Peer Reviewed
• [Journal Article] Identification of the H2-Kd-restricted cytotoxic T lymphocyte epitopes of a tumor-associated antigen, SPARC, which can stimulate antitumor immunity without causing autoimmune disease in mice (2009)
  • Author(s): Ikuta, Y., Hayashida, Y., Hirata, S., et al.
  • Journal Title: Cancer Sci 100(1) Pages: 132-137
  • NAID: 10025141633
  • Peer Reviewed
• [Journal Article] An in vivo model of priming of antigen-specific human CTL by Mo-DC in NOD/Shi-scid IL2rgamma(null)(NOG)mice (2009)
  • Author(s): Inoue, M., Senju, S., Hirata, S., et al
  • Journal Title: Immunol Lett 126 Pages: 67-72
  • Peer Reviewed
• [Journal Article] Efficient induction of human T-cell leukemia virus-1-specific CTL by chimeric particle without adjuvant as a prophylactic for adult T-cell leukemia (2009)
  • Author(s): Kozako, T., Fukuda, K., Hirata, S., et al.
  • Journal Title: Mol Immunol 47 Pages: 606-613
  • Peer Reviewed
• [Journal Article] TRAIL発現樹状細胞によるレギュラトリーT細胞の誘導と実験的自己免疫性脳脊髄炎の治療 (2009)
  • Author(s): 平田真哉、西村泰治
  • Journal Title: 臨床免疫・アレルギー科 51
  • NAID: 40016464329
• [Journal Article] Activation of antigen-specific cytotoxic T lymphocytes by beta 2-microglobulin or TAP1 gene disruption and the introduction of recipient-matched MHC class I gene in allogeneic embryonic stem cell-derived dendritic cells. (2008)
  • Author(s): Matsunaga, Y., Fukuma, D., Hirata, S., Fukushima, S., Haruta, M., Ikeda, T., Negishi, I., Nishimura, Y., Senju S.
  • Journal Title: J Immunol 181(9) Pages: 6635-43
  • Peer Reviewed
• [Journal Article] Identification of a novel tumor-associated antigen, cadherin 3/P-cadherin, as a possible target for immunotherapy of pancreatic, gastric, and colorectal cancers. (2008)
  • Author(s): Imai, K., Hirata, S., Irie, A., Senju, S., Ikuta, Y., Yokomine, K., Harao, M., Inoue, M., Tsunoda, T., Nakatsuru, S., Nakagawa, H., Nakamura, Y., Baba, H., Nishimura Y.
  • Journal Title: Clin Cancer Res 14(20) Pages: 6487-95
  • Peer Reviewed
• [Journal Article] HLA-A2-restricted CTL epitopes of a novel lung cancer-associated cancer testis antigen, cell division cycle associated 1, can induce tumor-reactive CTL. (2008)
  • Author(s): Harao, M., Hirata, S., Irie, A., Senju, S., Nakatsura, T., Komori, K., Ikuta, Y., Yokomine, K., Imai, K., Inoue, M., Harada, K., Mori, Y., Tsunoda, T., Nakatsuru, S., Daigo, Y., Nomori, H., Nakamura, Y., Baba, H., Nishimura, Y.
  • Journal Title: Int J Cancer 123(11) Pages: 2616-25
  • Peer Reviewed
• [Journal Article] Role of human non-invariant NKT lymphocytes in the maintenance of type 2 T helper environment during pregnancy. (2008)
  • Author(s): Uemura, Y., Suzuki, M., Liul, TY., Narita, Y., Hirata, S., Ohyama, H., Ishihara, O., Matsushita, S.
  • Journal Title: Int Immunol 20(3) Pages: 405-12
  • NAID: 10021239996
  • Peer Reviewed
• [Journal Article] Distinct subsets of human invariant NKT cells differentially regulate T helper responses via dendritic cells. (2008)
  • Author(s): Liu, TY., Uemura, Y., Suzuki, M., Narita, Y., Hirata, S., Ohyama, H., Ishihara, O., Matsushita, S.
  • Journal Title: Eur J Immunol 38(4) Pages: 1012-23
  • Peer Reviewed
• [Journal Article] ES-DC (2008)
  • Author(s): 平田真哉, 千住覚, 西村泰治
  • Journal Title: 炎症と-免疫(先端医学社(東京)) 16(1) Pages: 133-135
• [Journal Article] Distinct subsets of human invariant NKT cells differentially regulate T helper responses via dendritic cells (2008)
  • Author(s): Liu, TY., et.al.
  • Journal Title: Eur J Immunol 38 Pages: 1012-1023
  • Peer Reviewed
• [Journal Article] The transfer of ES cell-derived dendritic cells expressing TRAIL prolonged islets allograft survival.
  • Author(s): Hirata, S., Fukushima, S., Ikeda, T., Matsunaga, Y., Moriyama, H., Yokono, K., Nagata, M., Senju, S., Nishimura, Y.
  • Journal Title: Transplantation (in revision)
  • Peer Reviewed
• [Journal Article] Dual effects of TRAIL to suppress autoimmunity: the inhibition of Thl cells and thepromotion of regulatory T cells.
  • Author(s): Ikeda, T., Hirata, S., Fukushima, S., Matsunaga Y., Ito, T., Uchino, M., Nishimura, Y., Senju, S.
  • Journal Title: J Immunol (in revmision)
  • Peer Reviewed
• [Presentation] 免疫抑制性分子を遺伝子導入したマウスES細胞由来の樹状細胞の同種異系(アロ)移植への応用 (2008)
  • Author(s): 平田真哉, ら
  • Organizer: 第36回日本臨床免疫学会総会
  • Place of Presentation: 東京
• [Presentation] TRAILを発現するアロES-DCの投与によるアロ膵島に対する拒絶反応の抑制 (2008)
  • Author(s): 平田真哉, ら
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Remarks]
  • URL: http://www.tmd.ac.jp/grad/rheu/rheu-J.htm
• [Remarks]
  • URL: http://www.medic.kumamoto-u.ac.jp/dept/immunoge/immunoge.html