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Development of iPSC-derived T cells with antigen-specific helper or regulatory function

Research Project

Project/Area Number 26670578
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General surgery
Research InstitutionKyoto University

Principal Investigator

Kaneko Shin  京都大学, iPS細胞研究所, 准教授 (40361331)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsiPS細胞 / 再分化T細胞 / CD4T細胞 / T-iPS細胞 / 免疫再生 / 免疫制御 / 同種移植 / T細胞分化 / 移植免疫 / 抗原特異的T細胞 / 再生T細胞
Outline of Final Research Achievements

Three different antigen specific CD4 T cell clones are isolated from human peripheral blood and reprogrammed into T-iPS cells. For the purpose of induce HLA Class II restricted TCR expressing antigen specific T cells with helper function or regulatory function, current T cell differentiation protocol from iPS cell was optimized. Those T cells induced by the protocol showed HLA-class II restricted antigen specific proliferation and cytokine production. In addition, such HLA Class II restricted TCR expressing re-differentiated T cells showed an adjuvant function to induce antigen-specific CD8 CTLs for desired antigen via matulation of dendritic cells. The adjuvant effect was similar to teh effect induced by Type I helper T cells.

Academic Significance and Societal Importance of the Research Achievements

がん治療における免疫反応の重要性は広く知られるところである。iPS細胞は抗原特異的CD8キラーT細胞再生のソースとして期待されているが、抗原特異的CD4の再生についての報告はない。本研究では、抗原特異的TCRを発現しヘルパー機能をもつCD4発現細胞をiPS細胞から誘導することに成功した。キラーT細胞との併用により、治療効果の向上が期待できる。

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (46 results)

All 2016 2015 2014 Other

All Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (32 results) (of which Int'l Joint Research: 4 results,  Invited: 15 results) Remarks (3 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Va24 Invariant NK T-like Cells from Human Induced Pluripotent Stem Cells2016

    • Author(s)
      Kitayama S, Zhang R, Liu TY, Ueda N, Iriguchi S, Yasui Y, Kawai Y, Tatsumi M, Hirai N, Mizoro Y, Iwama T, Watanabe A, Nakanishi M, Kuzushima K, Uemura Y, Kaneko S
    • Journal Title

      Stem Cell Reports

      Volume: 6 Issue: 2 Pages: 213-227

    • DOI

      10.1016/j.stemcr.2016.01.005

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hepatocellular carcinoma cell sensitivity to Vg9Vd2 T lymphocyte-mediated killing is increased by zoledronate.2016

    • Author(s)
      Sugai S, Yoshikawa T, Iwama T, Tsuchiya N, Ueda N, Fujinami N, Shimomura M, Zhang R, Kaneko S, Uemura Y, Nakatsura T.
    • Journal Title

      Int J Oncol.

      Volume: 48 (5) Issue: 5 Pages: 1794-1804

    • DOI

      10.3892/ijo.2016.3403

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reprogramming away from the exhausted T cell state.2016

    • Author(s)
      Karagiannis P, Iriguchi S, Kaneko S.
    • Journal Title

      Seminar in Immunology

      Volume: In press Issue: 1 Pages: 71-78

    • DOI

      10.1016/j.smim.2015.10.007

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] BCR-ABL-specific CD4+ T helper cells promote the priming of antigen-specific cytotoxic T cells via dendritic cells.2016

    • Author(s)
      Ueda N, Zhang R, Tatsumi M, Liu TY, Kitayama S, Yasui Y, Sugai S, Senju S, Kuzushima K, Kiyoi H, Kaneko S, Uemura Y.
    • Journal Title

      Cellular and Molecular Immunology

      Volume: In Press

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 多能性幹細胞のT細胞研究への応用2015

    • Author(s)
      上田樹、金子新
    • Journal Title

      日本臨床免疫学会雑誌

      Volume: 38(2) Pages: 101-108

    • NAID

      130005072692

    • Related Report
      2015 Annual Research Report
    • Open Access
  • [Journal Article] T-cell-restricted T-bet overexpression induces aberrant hematopoiesis of myeloid cells and impairs function of macrophages in the lung2015

    • Author(s)
      Iriguchi S, Kikuchi N, Kaneko S, Noguchi E, Morishima Y, Matsuyama M, Yoh K, Takahashi S, Nakauchi H, Ishii Y
    • Journal Title

      Blood

      Volume: 125 Issue: 2 Pages: 370-82

    • DOI

      10.1182/blood-2014-05-575225

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] iPS細胞技術による腫瘍免疫・感染免疫の再生2015

    • Author(s)
      金子新
    • Journal Title

      実験医学

      Volume: 33(2) Pages: 115-120

    • Related Report
      2014 Research-status Report
  • [Journal Article] Rise of iPSCs as a cell source for adoptive immunotherapy.2014

    • Author(s)
      Minagawa A, Kaneko S.
    • Journal Title

      Hum Cell.

      Volume: 27 Issue: 2 Pages: 47-50

    • DOI

      10.1007/s13577-014-0089-8

    • NAID

      120005650279

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] iPS細胞を用いた免疫細胞のin vitro再生2014

    • Author(s)
      金子新
    • Journal Title

      医学のあゆみ

      Volume: 251(8) Pages: 643-648

    • Related Report
      2014 Research-status Report
  • [Presentation] ゲノム編集を利用した、iPS細胞よりの抗原特異的免疫細胞の再生2016

    • Author(s)
      南川淳隆
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2016-03-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] iPS細胞を介した抗原特異的T細胞の再生2016

    • Author(s)
      金子新
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2016-03-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 生物由来原料フリーの培養系を用いたヒトiPS細胞からのT細胞再分化系の構築2016

    • Author(s)
      安井裕
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2016-03-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] iPS細胞を介したT細胞の再生と治療開発2016

    • Author(s)
      金子新
    • Organizer
      第31回新潟血液免疫疾患研究会
    • Place of Presentation
      新潟
    • Year and Date
      2016-02-26
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 新たながん免疫療法-T細胞の再生2015

    • Author(s)
      金子新
    • Organizer
      第86回日本呼吸器学会・第116回日本結核病学会近畿地方会
    • Place of Presentation
      京都
    • Year and Date
      2015-12-19
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] iPS細胞を利用したがん免疫治療の開発2015

    • Author(s)
      金子新
    • Organizer
      第6回筑波大学附属病院茨城県地域医療臨床教育センター講演会
    • Place of Presentation
      筑波
    • Year and Date
      2015-12-10
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Generation of BCR-ABL Reactive CD4+ T Helper Cells By Reprograming and Redifferentiation.2015

    • Author(s)
      Ueda N.,Uemura Y., Rhong Z., Kitayama S., Yasui Y., Tatsumi M., Liu T, Y., Kuzushima K., Kiyoi H., Naoe T., Kaneko S.
    • Organizer
      The 57th ASH Annual Meeting and Exposition
    • Place of Presentation
      Orland,USA
    • Year and Date
      2015-12-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] iPS細胞に由来する再生T細胞療法の開発2015

    • Author(s)
      金子新
    • Organizer
      千里ライフサイエンスセミナー「がん免疫療法の進展と将来展望」
    • Place of Presentation
      豊中
    • Year and Date
      2015-11-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Reprogramming and redifferentiation of antigen specific T cells by iPS cell technology.2015

    • Author(s)
      金子新
    • Organizer
      Tsukuba Hematology Seminar
    • Place of Presentation
      筑波
    • Year and Date
      2015-11-21
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Generation of BCR-ABL reactive CD4 T lymphocytes by reprograming and redifferentiation.2015

    • Author(s)
      Ueda N.,Uemura Y., Rhong Z., Kitayama S., Yasui Y., Tatsumi M., Liu T, Y., Kuzushima K., Kiyoi H., Naoe T., Kaneko S.
    • Organizer
      第44回日本免疫学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      2015-11-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] iPS細胞を介した抗原特異的T細胞の再生2015

    • Author(s)
      金子新
    • Organizer
      第43回日本臨床免疫学会スイーツセミナー
    • Place of Presentation
      神戸
    • Year and Date
      2015-10-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Optimization of Xeno-Free culture system for in vitro induction of T cells from human iPS cells.2015

    • Author(s)
      安井裕
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] Generation of BCR-ABL reactive CD4 T lymphocytes by reprograming and redifferentiation.2015

    • Author(s)
      上田格弘
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] iPS細胞由来BCR-ABL特異的CD4陽性T細胞によるCML新規免疫療法の開発2015

    • Author(s)
      上田格弘、植村靖史、張エイ、喜多山秀一、安井裕、巽美奈子、劉天懿、須貝詩織、葛島清隆、清井仁 、金子新
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] iPS細胞を活用した抗原特異的T細胞療法の開発2015

    • Author(s)
      安井裕
    • Organizer
      第7回血液疾患免疫療法研究会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-09-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] iPS細胞技術のがん治療への応用2015

    • Author(s)
      金子新
    • Organizer
      第13回ペイシェント・アクティブ・フォーラム
    • Place of Presentation
      東京
    • Year and Date
      2015-09-23
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] T-cell-restrcted T-bet overexpression induces aberrant hematopoiesis of myeloid cells and impairs function of macrophages in the lung.2015

    • Author(s)
      Iriguchi S.
    • Organizer
      第44回国際実験血液学ミーティング
    • Place of Presentation
      京都
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] T-cell-restrcted T-bet overexpression induces aberrant hematopoiesis of myeloid cells and impairs function of macrophages in the lung.2015

    • Author(s)
      Iriguchi S.
    • Organizer
      第11回血液学若手研究者勉強会(麒麟塾)
    • Place of Presentation
      東京
    • Year and Date
      2015-07-11
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Optimization of Xeno-Free culture sytem for in vitro induction of T cells from human induced pluripotent stem cells.2015

    • Author(s)
      Yasui Y.
    • Organizer
      International Society for Stem Cell Research
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2015-06-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Making anti cancer effector cells derived from iPSCs by T-cell receptor transfer.2015

    • Author(s)
      Minagawa A.
    • Organizer
      International Society for Stem Cell Research
    • Place of Presentation
      Stockholm, Sweden
    • Year and Date
      2015-06-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Generation of adaptive and innate-like lymphoid killer cells from a single T-iPSC.2015

    • Author(s)
      河合洋平
    • Organizer
      Kyoto T Cell Conference
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2015-05-16
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] iPS細胞技術を用いて再生した抗原特異的T細胞の特性2015

    • Author(s)
      金子新
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2015-03-21
    • Related Report
      2014 Research-status Report
  • [Presentation] Generation of immune cells from human iPS cell.2015

    • Author(s)
      金子新
    • Organizer
      第18回武田科学振興財団生命科学シンポジウム/CiRA第18回International Symposium
    • Place of Presentation
      吹田
    • Year and Date
      2015-01-16
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Generation of BCR-ABL reactive CD4 T lymphocytes by reprograming and redifferentiation2014

    • Author(s)
      UEDA Norihiro, UEMURA Yasushi, ZHANG Rong, LIU Tian-Yi, TATSUMI Minako, YASUI Yutaka, KUZUSHIMA Kiyotaka, KIYOI Hitoshi, KANEKO Shin.
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Research-status Report
  • [Presentation] iPS細胞を用いた免疫細胞の再生2014

    • Author(s)
      金子新
    • Organizer
      第28回日本エイズ学会学術集会・総会
    • Place of Presentation
      大阪
    • Year and Date
      2014-12-03
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] BCR-ABL-specific T helper cells facilitate propagation of antigen-specific CTLs via DC maturation2014

    • Author(s)
      上田格弘、植村靖史、張エイ、劉天懿、巽美奈子、安井裕、葛島清隆、清井仁、金子新
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Research-status Report
  • [Presentation] iPS細胞技術を利用したT細胞の再生と臨床応用の展望2014

    • Author(s)
      金子新
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Generation of BCR-ABL reactive CD4 Tlymphocytes by reprograming and redifferentiation2014

    • Author(s)
      Norihiro Ueda, Yasushi Uemura, Rong Zhang, Tianyi Liu, Minako Tatsumi, Yutaka Yasui, Kiyotaka Kuzushima, hitoshi Kiyoi, Shin Kaneko.
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Reprogramming and regeneration of antigen-specific killer T cells2014

    • Author(s)
      Shin Kaneko
    • Organizer
      The 10th Annual Meeting of Korean Society for Stem Cell Reserach
    • Place of Presentation
      Soul Korea
    • Year and Date
      2014-08-28
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] BCR-ABL 特異的ヘルパーT細胞のリプログラミングとCML治療への応用2014

    • Author(s)
      上田格弘、植村靖史、張エイ、劉天懿、巽美奈子、安井裕、葛島清隆、清井仁、金子新
    • Organizer
      第18回日本がん免疫学会総会
    • Place of Presentation
      愛媛
    • Year and Date
      2014-07-30 – 2014-08-01
    • Related Report
      2014 Research-status Report
  • [Presentation] Regeneration of immune cells for immunotherapy2014

    • Author(s)
      金子新
    • Organizer
      第12回幹細胞シンポジウム
    • Place of Presentation
      福岡
    • Year and Date
      2014-05-30
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Human immune cells form induced pluripotent stem cells2014

    • Author(s)
      金子新
    • Organizer
      Joint JAPAN-US conference in iPS and cancer
    • Place of Presentation
      京都
    • Year and Date
      2014-04-17
    • Related Report
      2014 Research-status Report
    • Invited
  • [Remarks] 京都大学iPS細胞研究所

    • URL

      http://www.cira.kyoto-u.ac.jp/

    • Related Report
      2015 Annual Research Report
  • [Remarks] 金子研究室ホームページ

    • URL

      http://www.cira.kyoto-u.ac.jp/kaneko/index.html

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
  • [Remarks] 京都大学iPS細胞研究所 CiRA(サイラ)

    • URL

      https://www.cira.kyoto-u.ac.jp/j/index.html

    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] 多能性幹細胞から免疫細胞療法用T細胞を誘導する方法2015

    • Inventor(s)
      金子新、南川淳隆、堀田秋津、河本宏、増田橋子、島津裕、一瀬大志
    • Industrial Property Rights Holder
      国立大学法人京都大学、アストリム株式会社
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-07-17
    • Related Report
      2015 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] CD4陽性細胞の製造方法2015

    • Inventor(s)
      金子新、上田格弘、植村靖史
    • Industrial Property Rights Holder
      国立大学法人京都大学、国立研究開発法人国立がん研究センター
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-203482
    • Filing Date
      2015-11-13
    • Related Report
      2015 Annual Research Report

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Published: 2014-04-04   Modified: 2020-03-30  

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