Immune-regulation therapy with ES cell-derived dendritic cells

• Project/Area Number: 19591172
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Kumamoto University
• Principal Investigator: SENJU Satoru Kumamoto University, 大学院・医学薬学研究部, 准教授 (50274709)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 樹状細胞 / ES細胞 / 免疫制御 / MHC / 細胞治療 / T細胞 / 悪性腫瘍 / 抗原提示 / 遺伝子標的破壊 / 遺伝子治療

Research Abstract

我々は、ES細胞由来の樹状細胞(ES-DC)を用いた細胞ワクチン技術の開発を行っている。ES細胞に由来する細胞を用いた医療において問題となる、HLAのミスマッチを解決する方法を検討すべく研究を行った。未分化なマウスES細胞に遺伝的改変を行い、β2-microglobulin(β2m)遺伝子、あるいはTAP1遺伝子の標的破壊を行ったものに、さらに、高濃度薬剤選択により、これらの遺伝子をホモ接合として欠損したマウスES細胞を作製した。そして、これらのES細胞に由来するES-DCをアロのレシピエントに移入し機能解析を行った。

Research Products

• [Journal Article] Identification of the H2-K^d-restricted cytotoxic T lymphocytes 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., and Nishimura, Y. (*these two authors contributed equally.)
  • Journal Title: Cancer Science 100 Pages: 132-137
  • NAID: 10025141633
  • 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. Clin (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., and Nishimura, Y.
  • Journal Title: Cancer Res 14 Pages: 6487-6495
  • Peer Reviewed
• [Journal Article] Activation of antigen-specific cytotoxic T lymphocytes by・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, H., Fukushima, S., Haruta, M., Ikeda, T., Negishi, I., Nishimura, Y. and Senju, S.
  • Journal Title: J. Immunol 181 Pages: 6635-6643
  • Peer Reviewed
• [Journal Article] B-Raf-mediated signaling pathway regulates T cell development. Eur (2008)
  • Author(s): Tsukamoto, H., Irie, A., Senju, S., Hatzopoulos, A.K., Wojnowski, L. and Nishimura, Y.
  • Journal Title: J. Immunol 38 Pages: 518-527
  • 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. Int (2008)
  • Author(s): Harao, M., Hirata, S., Irie, A., Senju, S., Nakatsura, T., Komori, H., Ikuta, Y., Yokomine, K., Imai, K., Inoue, M., Harada, K., Mori, T., Tsunoda, T., Nakatsuru, S., Daigo, Y., Nomori, H., Nakamura, Y., Baba, H., Nishimura, Y.
  • Journal Title: J. Cancer 123 Pages: 2616-2625
  • Peer Reviewed
• [Journal Article] Activation of antigen-specific cytotoxic T lymphocytes by β2-microglobulin or TAP1 gene disruption and the introduction of recipient-matched MHC class I gene in allogeneic ES cell-derived dendritic cells. (2008)
  • Author(s): Matsunaga, Y., et al.
  • Journal Title: J. Immunol. 181 Pages: 6635-6643
  • 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., et al.
  • Journal Title: Clin. Cancer Res. 14 Pages: 6487-6495
  • 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., et al.
  • Journal Title: Int. J. Cancer. 123 Pages: 2616-2625
  • Peer Reviewed
• [Journal Article] Identification of the H2-Kd-restricted CTL epitopes of a tumor-associated antigen. SPARC, which can stimulate antitumor immunity without causing autoimmune disease in mice. (2008)
  • Author(s): Ikuta, Y., et al.
  • Journal Title: Cancer Science. 100 Pages: 132-137
  • Peer Reviewed
• [Journal Article] B-Raf-mediated signaling pathway regulates T cell development. (2008)
  • Author(s): Tsukamoto, H., et al.
  • Journal Title: Eur. J. Immunol. 38 Pages: 513-527
  • Peer Reviewed
• [Journal Article] B-Raf-mediated signaling pathway regulates T cell development. (2008)
  • Author(s): Tsukamoto, H., et. al.
  • Journal Title: Eur. J. Immunol 38 Pages: 518-527
  • Peer Reviewed
• [Journal Article] 医学用語解説「ES-DC」 (2008)
  • Author(s): 平田 真哉
  • Journal Title: 炎症と免疫 98 Pages: 133-135
  • Peer Reviewed
• [Journal Article] Genetically manipulated human embryonic stem cell-derived dendritic cells with immune regulatory function (2007)
  • Author(s): Senju, S., Suemori, H., Zembutsu, H., Uemura, Y., Hirata, S., Fukuma, D., Matsuyoshi, H., Shimomura, M., Haruta, M., Fukushima, S., Matsunaga, Y., Katagiri, T., Nakamura, Y., Furuya, M., Nakatsuji, N., and Nishimura, Y.
  • Journal Title: Stem cells 25 Pages: 2720-2729
  • Peer Reviewed
• [Journal Article] Regression of intestinal adenomas by vaccination with heat shock protein 105-pulsed bone marrow-derived dendritic cells in ApcMin/+ mice (2007)
  • Author(s): Yokomine, K., Nakatsura, T., Senju, S., Nakagata, N., Minohara, M, Kira, J., Motomura, Y., Kubo, T., Sasaki, Y., and Nishimura, Y.
  • Journal Title: Cancer Science 98 Pages: 1930-1935
  • NAID: 10019996483
  • Peer Reviewed
• [Journal Article] Involvement of regulatory T cells in the experimental autoimmune encephalomyelitis-preventive effect of dendritic cells expressing myelin oligodendrocyte glycoprotein plus TRAIL (2007)
  • Author(s): Hirata, S., Matsuyoshi, H., Fukuma, D., Kurisaki, A., Uemura, Y., Nishimura, Y.* and Senju, S.* (*equal contribution)
  • Journal Title: J. Immunol 178 Pages: 918-925
  • Peer Reviewed
• [Journal Article] Genetically manipulated human embryonic stem cell-derived dendritic cells with immune regulatory function. (2007)
  • Author(s): Senju, S., et. al.
  • Journal Title: Stem cells 25 Pages: 2720-2729
  • Peer Reviewed
• [Journal Article] Involvement of regulatory T cells in the experimental autoimmune encephalomyelitis- preventive effect of dendritic cells expressing myelin oligodendrocyte glycoprotein plus TRAIL. (2007)
  • Author(s): Hirata, S., et. al.
  • Journal Title: J. Immunol 178 Pages: 918-925
  • Peer Reviewed
• [Journal Article] 第12章「T細胞応答の抑制性制御」 (2007)
  • Author(s): 千住 覚
  • Journal Title: 免疫応答と免疫病態の統合的分子理解 Pages: 116-122
• [Journal Article] MHCとは何か (2007)
  • Author(s): 千住 覚
  • Journal Title: アニテックス19(2)特集「動物MHC」 Pages: 3-8
• [Journal Article] Characterization of dendritic cells and macrophages generated by directed differentiation from mouse induced pluripotent stem cells
  • Author(s): Senju, S., Haruta, M., Matsunaga, Y., Fukushima, S., Ikeda, T., Takahashi, K., Okita, K., Yamanaka, S., and Nishimura, Y.
  • Journal Title: Stem Cells (in press)
  • Peer Reviewed
• [Journal Article] Multiple antigen-targeted immunotherapy with alpha-galactosylceramide-loaded and genetically engineered dendritic cells derived from embryonic stem cells
  • Author(s): Fukushima, S., Hirata, S., Motomura, Y., Fukuma, D., Matsunaga, Y., Ikuta, Y., Ikeda, T., Kageshita, T., Ihn, H., Nishimura, Y.and Senju, S.
  • Journal Title: J.Immunotherapy (in press)
  • Peer Reviewed
• [Journal Article] Characterization of dendritic cells and macrophages generated by directed differentiation from mouse induced pluripotent stem cells.
  • Author(s): Senju, S., et al.
  • Journal Title: Stem Cells. (in press)
  • Peer Reviewed
• [Journal Article] Multiple antigen-targeted immunotherapy with a-galactosylceramide-loaded and genetically engineered dendritic cells derived ftom embryonic Stern cells.
  • Author(s): Fukushima, S., et al.
  • Journal Title: J. Immunotherapy (in press)
  • Peer Reviewed
• [Presentation] Effective immunotherapy with・-GalCer-loaded embryonic stem cell-derived dendritic cells expressing antigens against B16 melanoma (2008)
  • Author(s): 千住覚
  • Organizer: International Investigative Darmatology
  • Place of Presentation: 京都
• [Presentation] ES細胞およびiPS細胞由来の免疫細胞を用いた医療技術の開発 (2008)
  • Author(s): 千住覚
  • Organizer: 第32回阿蘇シンポジウム
  • Place of Presentation: 熊本
• [Presentation] 免疫細胞療法への応用を目指したマウスiPS細胞からの樹状細胞の作製技術の開発 (2008)
  • Author(s): 千住覚
  • Organizer: 第17回日本組織適合性学会大会
  • Place of Presentation: 大阪
• [Presentation] 免疫細胞療法への応用を目指したマウスiPS細胞からの樹状細胞の分化誘導 (2008)
  • Author(s): 千住覚
  • Organizer: 人類遺伝学会第53回大会
  • Place of Presentation: 横浜
• [Presentation] Immunotherapy with multiple antigen-targeted and α-galactosylcer amide-loaded dendritic cells derived from embryonic stem cells (2008)
  • Author(s): 千住覚
  • Organizer: 第10回国際樹状細胞シンポジウム
  • Place of Presentation: 神戸
• [Presentation] Genetic modifications of ES cell-derived DC to modify cell surface MHC class (2008)
  • Author(s): 千住覚
  • Organizer: 第10回国際樹状細胞シンポジウム
  • Place of Presentation: 神戸
• [Presentation] 進行性幹細胞がん患者に対するGlypican-3ペプチドワクチンの臨床第1相試験での安全性と有効性 (2008)
  • Author(s): 千住覚
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 肺癌に高発現する新規癌精巣抗原CDCA1を標的とした癌免疫療法の開発 (2008)
  • Author(s): 千住覚
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 膵癌の免疫療法に有用な新規癌関連抗原CDH3の同定 (2008)
  • Author(s): 千住覚
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [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異種系(アロ)移植への応用 (2008)
  • Author(s): 千住覚
  • Organizer: 第36回日本臨床免疫学会
  • Place of Presentation: 東京
• [Presentation] 複数抗原を標的とし、α-GalCerを負荷した遺伝子導入ES細胞由来樹状細胞を用いた癌免疫療法 (2008)
  • Author(s): 千住覚
  • Organizer: 第36回日本臨床免疫学会
  • Place of Presentation: 東京
• [Presentation] 複数抗原を標的としたα-GalCer負荷ES細胞由来樹状細胞による癌免疫療法 (2008)
  • Author(s): 千住覚
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] Activation of antigen-specific CTL by β2-microgloblin or TAP1 gene-disrupted and recipient-matched MHC class I gene-introduced allogeneic ES cell-derived dentritic cells (2008)
  • Author(s): 千住覚
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] TRAI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): 千住覚
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] マウスiPS細胞からの樹状細胞の作製 (2008)
  • Author(s): 千住覚
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] Establishment of hu-SCID mouse system to analize priming in vivo of antigen-specific human CTLs by DC (2008)
  • Author(s): 千住覚
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] SARS-Cov slike protein-derived HLA-A2-restricted CTL epitope identified by using HLA-A2/Db-transgenic mice (2008)
  • Author(s): 千住覚
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] Effective immunotherapy with a-GalCer-loaded embryonic stem cell-derived dendritic cells expressing multiple antigens against B16 melanoma. (2008)
  • Author(s): 千住 覚, 他
  • Organizer: International Investigative Dermatology
  • Place of Presentation: 京都
• [Presentation] 免疫細胞療法への応用を目指したマウスiPS細胞からの樹状細胞の作製技術の確立 (2008)
  • Author(s): 千住 覚, 他
  • Organizer: 第17回日本組織適合性学会大会
  • Place of Presentation: 大阪
• [Presentation] Immunotherapy with multiple antigen-targeted and α-galactosylceramide-loaded dendritic cells deived from embryonic stem cells. (2008)
  • Author(s): 千住 覚, 他
  • Organizer: 第10回国際樹状細胞シンポジウム
  • Place of Presentation: 神戸
• [Presentation] Genetic modifications of ES cell-derived DC to modify cell surface MHC class. (2008)
  • Author(s): 千住 覚, 他
  • Organizer: 第10回国際樹状細胞シンポジウム
  • Place of Presentation: 神戸
• [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): 千住 覚, 他
  • Organizer: 第36回日本臨床免疫学会
  • Place of Presentation: 東京
• [Presentation] 複数抗原を標的とし、αGalCerを負荷した遺伝子導入ES細胞由来樹状細胞を用いた癌免疫療法 (2008)
  • Author(s): 千住 覚, 他
  • Organizer: 第36回日本臨床免疫学会
  • Place of Presentation: 東京
• [Presentation] Activation of antigen-specific CTL by β2-microglobulin or TAP1 gene-disrupted and recipient-matched MHC class I gene-introduced allogeneic ES cell-derived dentritic cells. (2008)
  • Author(s): 千住 覚, 他
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [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): 千住 覚, 他
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] Establishment of hu-SCID mouse system to analuze priming in vivo of antigen-specific human CTLs by DC. (2008)
  • Author(s): 千住 覚, 他
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] SARS-Cov spike protein-derived HLA-A2-restricted CTL epitope identified by using HLA-A2/Db-transgenic mice. (2008)
  • Author(s): 千住 覚, 他
  • Organizer: 第38回日本免疫学会総会・学術集会(京都)
  • Place of Presentation: 京都
• [Presentation] Disruption of the TAP1 or [○!R]2-microgloblin gene in ES cells to overcome the histoincompatibility between ES-DC and the recipients (2007)
  • Author(s): 松永雄亮
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] MOGペプチドとTRAILを共発現する樹状細胞による制御性T細胞を介したEAEの発症抑制 (2007)
  • Author(s): 平田真哉
  • Organizer: 第35回日本臨床免疫学会総会
  • Place of Presentation: 大阪
• [Presentation] 遺伝子導入ヒトES細胞から分化誘導した樹状細胞による免疫調節能の発現 (2007)
  • Author(s): 千住覚
  • Organizer: 日本人類遺伝学会第52回大会
  • Place of Presentation: 東京
• [Presentation] 抗原提示機能を有するヒトES細胞由来の樹状細胞(ヒトES-DC)の確立 (2007)
  • Author(s): 千住覚
  • Organizer: 第16回日本組織適合性学会大会
  • Place of Presentation: 京都
• [Presentation] Genetic engineering of human embryonic stem cell-derived dendritic cells (2007)
  • Author(s): 千住覚
  • Organizer: 13^<th> International Congress of Immunology
  • Place of Presentation: ブラジル・リオデジャネイロ
• [Presentation] Important roles of B-Raf in T cell development and TCR-ligand avidity-sensitive T cell activation (2007)
  • Author(s): 塚本博丈
  • Organizer: 13^<th> International Congress of Immunology
  • Place of Presentation: ブラジル・リオデジャネイロ
• [Presentation] 抗原提示機能を有するヒトES細胞由来の樹状細胞 (2007)
  • Author(s): 千住覚
  • Organizer: Kyoto T Cell Conference
  • Place of Presentation: 京都
• [Presentation] Genetic engineering of human embryonic stem cell-derived dendritic cells (2007)
  • Author(s): Senju, S.
  • Organizer: 13^<th> International Congress of Immunology
  • Place of Presentation: リオデジャネイロ (ブラジル)
• [Presentation] Important roles of B-Raf in T cell development and TCR-ligandavidity-sensitiveT cell activation (2007)
  • Author(s): Tsukamoto, H.
  • Organizer: 13^<th> International Congress of Immunology
  • Place of Presentation: リオデジャネイロ (ブラジル)
• [Presentation] 抗原提示機能を有するヒトES細胞由来の樹状細胞(ヒトES・DC)の樹立 (2007)
  • Author(s): 千住 覚
  • Organizer: 第16回日本組織適合性学会大会
  • Place of Presentation: 京都
• [Presentation] 遺伝子導入ヒトES細胞から分化誘導した樹状細胞による 免疫調節能の発現 (2007)
  • Author(s): 千住 覚
  • Organizer: 日本人類遺伝学会 第52回大会
  • Place of Presentation: 東京
• [Presentation] MOGペプチドとTRAILIを共発現する樹状細胞による制御性T細胞を介したEAEの発症抑制 (2007)
  • Author(s): 平田 真哉
  • Organizer: 第35回日本臨床免疫学会総会
  • Place of Presentation: 大阪
• [Presentation] Disruption of the TAP1 or β2-microgloblin gene in ES cells to overcome the histoincompatibility between ES-DC and the recipients (2007)
  • Author(s): MATSUNAGA Yusuke
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
• [Book] HLA分子による癌特異抗原の提示を利用した癌免疫療法の開発 (2008)
  • Author(s): 千住覚
  • Publisher: MHC(日本組織適合性学会)
• [Book] ES細胞由来の樹状細胞による抗腫瘍免疫応答の誘導 (2008)
  • Author(s): 千住覚
  • Publisher: 腫瘍内科(科学評論社)
• [Book] iPS細胞由来の樹状細胞とマクロファージを用いた医療技術の開発 (2008)
  • Author(s): 千住覚
  • Publisher: 再生医療(メディカルレビュー社)
• [Book] 新規癌胎児性抗原Glypican-3の肝細胞癌の診断と免疫療法への応用 (2008)
  • Author(s): 西村泰治、千住覚
  • Publisher: Jpn. J. Clin. Immunol.(小宮山印刷工業株式会社)
• [Book] ES細胞およびiPS細胞を用いた免疫療法 (2008)
  • Author(s): 千住覚
  • Publisher: 医学のあゆみ(医歯薬出版)
• [Book] 免疫療法への応用を目指したES細胞からの樹状細胞の作製 (2008)
  • Author(s): 千住覚
  • Publisher: 実験医学(羊土社)
• [Book] 医学用語解説ES-DC (2008)
  • Author(s): 平田真哉、千住覚、西村泰治
  • Publisher: 炎症と免疫(先端医学社)
• [Book] HLA分子による癌特異抗原の提示を利用した癌免疫療法の開発 (2008)
  • Author(s): 千住 覚
  • Publisher: 日本組織適合性学会誌
• [Book] ES細胞由来の樹状細胞による抗腫瘍免疫応答の誘導 (2008)
  • Author(s): 千住 覚
  • Publisher: 腫瘍内科
• [Book] iPS細胞由来の樹状細胞とマクロファージを用いた医療技術の開発 (2008)
  • Author(s): 千住 覚
  • Publisher: 再生医療
• [Book] 新規癌胎児性抗原Glypican-3の肝細胞癌の診断と免疫療法への応用 (2008)
  • Author(s): 西村泰治
  • Publisher: Jpn. J. Clin. Immunol.
• [Book] ES細胞およびiPS細胞を用いた免疫療法 (2008)
  • Author(s): 千住 覚
  • Publisher: 医学のあゆみ
• [Book] 免疫療法への応用を目指したES細胞からの樹状細胞の作製 (2008)
  • Author(s): 千住 覚
  • Publisher: 実験医学(羊土社)
• [Book] 第12章T細胞応答の抑制性制御 (2007)
  • Author(s): 千住覚、西村泰治
  • Publisher: 免疫応答と免疫病態の統合的分子理解(南山堂)
• [Book] 19(2)特集動物MHC「MHCとはなにか」 (2007)
  • Author(s): 千住覚、西村泰治
  • Publisher: アニテックス(研成社)