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2012 Fiscal Year Final Research Report

Development of cellular cancer immunotherapy by using humaniPS-cell-derived dendritic cells and ideal cancer-associated antigens

Research Project

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Project/Area Number 23650609
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor immunology
Research InstitutionKumamoto University

Principal Investigator

NISHIMURA Yasuharu  熊本大学, 大学院・生命科学研究部, 教授 (10156119)

Co-Investigator(Kenkyū-buntansha) AWAI Hirotake  熊本大学, 大学院・生命科学研究部, 助教 (10433020)
Project Period (FY) 2011 – 2012
KeywordsiPS 細胞 / 樹状細胞 / がん抗原 / 腫瘍免疫 / がん免疫療法 / T 細胞
Research Abstract

We established a method by which we can obtain a large number of functional dendritic cells (DC)with a simple procedure from human iPS cells. We transduced iPS cell-derived CD11b+myeloid cellswith cMYC and BMI1 genes associated with proliferative or anti-senescence effects. This made the cellscapable of propagating for more than 4 months in an M-CSF-dependent manner while retaining thecapacity to differentiate into DC. We named the iPS cell-derived proliferating myeloid cells “iPS-ML”,and the iPS-ML-derived dendritic cells “ML-DC”. In addition, we generated T AP2-deficient iPS cellclones by zinc finger nuclease-aided targeted gene disruption. T AP2-deficient iPS-ML avoidedrecognition by pre-activated allo-reactive CD8+T cells. The T AP2-deficient ML-DC expressingexogenously introduced HLA-A2 genes stimulated HLA-A2-restricted tumor antigen-specific CD8+Tcells obtained from HLA-A2-positive allogeneic donors, resulting in generation of tumorantigen-specific CTL lines. T AP-deficient iPS-ML introduced with various HLA class I genes may serveas an unlimited source of DC for vaccination therapy . Based on the present study , we propose aDC-producing system, which is simple, safe, and applicable to any patients irrespective of their HLAtypes. This technology will pave the way for the mass production of DC for therapeutic use. We havealso succeeded in inhibition of tumor growth of intraperitoneal dissemination of human cancer cells inimmune-deficient mice by intraperitoneal injection of human iPS-macrophage genetically modified tosecrete interferon-beta.

  • Research Products

    (16 results)

All 2013 2012 2011 Other

All Journal Article (7 results) (of which Peer Reviewed: 5 results) Presentation (8 results) Remarks (1 results)

  • [Journal Article] TAP-deficient human iPScell-derived myloid cell lines asunlimited cell source for dendriticcell-like antigen presenting cells.2013

    • Author(s)
      Haruta, M. Tomita, Y. Yuno A. MatumuraK. Ikeda T. Takamatsu K. Haga E. Koba C.Nishimura Y.
    • Journal Title

      GeneTherapy

      Volume: 20 Pages: 504-513

    • DOI

      DOI:10.1038/gt.2012.59

    • Peer Reviewed
  • [Journal Article] LA多型を考慮したがん免疫療法の開発2013

    • Author(s)
      冨田雄介、千住覚、入江厚、西村泰治
    • Journal Title

      日本組織適合性学会誌

      Volume: 20巻 Pages: 45-56

  • [Journal Article] Generation of dendriticcells and macrophages from human inducedpluripotent stem cells aiming at celltherapy2011

    • Author(s)
      Senju S, Haruta M, Matsunaga K,Fukushima S, Ikeda T, Takamatsu K, IrieA, Nishimura Y.
    • Journal Title

      Gene Therapy

      Volume: 18 Pages: 847-883

    • DOI

      DOI:10.1038/gt.

    • Peer Reviewed
  • [Journal Article] Immunotherapy withpluripotent stem cell-derived cells2011

    • Author(s)
      Seju S, Matsunaga K, Fukushima S, HirataS, Motomura Y, Fukuma D, Matsuyoshi H,Nishimura Y.
    • Journal Title

      Seminars in Immunopathology

      Volume: 33 Pages: 603-612

    • DOI

      DOI:10.1007/s00281-011-0263-y

    • Peer Reviewed
  • [Journal Article] がん抗原とα-GalCer を負荷した樹状細胞による腫瘍免疫の増強2011

    • Author(s)
      福島聡、千住覚、尹浩信、西村泰治
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 55巻 Pages: 262-268

  • [Journal Article] Generationof a large number of functional dendriticcells from human monocytes expanded byforced expression of cMYC plus BMI1

    • Author(s)
      Haruta, M., Tomita, Y., Imamura, Y.,Matsumura, K., Ikeda, T., Takamatsu, K.,Nishimura,Y., and Senju, S.
    • Journal Title

      Human Immunology

      Volume: (in press)

    • Peer Reviewed
  • [Journal Article] Therapeutic effect of human iPS-cellderived myeloid cells expressing IFN-β against peritoneally disseminatedcancer in xenograft models

    • Author(s)
      Koba, C. Haruta, M. Matsunaga, Y.Matsumura, K. Haga, E. Sasaki Y. Ikeda,T. Takamatsu, K. Nishimura, Y. and Senju,S.
    • Journal Title

      PLOS ONE

      Volume: (in press)

    • Peer Reviewed
  • [Presentation] TP2-deficient humaniPS cell-derived dendritic cells.2012

    • Author(s)
      千住覚、西村泰治
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Year and Date
      20121205-20121207
  • [Presentation] Cancerimmunotherapy using ideal Tumorassociated antigenic peptides and humaniPS cell derived dendritic cells2012

    • Author(s)
      Senju S., 他9名, Nishimura Y.
    • Organizer
      Centennial of Hashimoto Disease
    • Place of Presentation
      アクロス福岡 (福岡市)
    • Year and Date
      20121201-20121204
  • [Presentation] TAP 欠損ヒト iSP 細胞を用いたHLA オーダーメイド樹状細胞療法の開発2012

    • Author(s)
      西村泰治
    • Organizer
      日本人類遺伝学会第57回大会
    • Place of Presentation
      京王プラザホテル (東京都)
    • Year and Date
      20121025-20121027
  • [Presentation] CancerImmunotherapy using ideal tumorassociated antigenic peptides and humaniPS cell-derived dendritic cells2012

    • Author(s)
      Nishimura Y
    • Organizer
      The16th International HLA andImmunogenetics Conference
    • Place of Presentation
      リバプール(英国)
    • Year and Date
      20120531-20120603
  • [Presentation] Targeteddisruption of the TAP2 gene in human iPScells and generation of an infinitedendritic cell source that is applicableto vaccination therapy irrespective ofHLA types of the patients.2012

    • Author(s)
      Senju S., 他2名, Nishimura Y
    • Organizer
      The 16thInternational HLA and ImmunogeneticsConference
    • Place of Presentation
      リバプール(英国)
    • Year and Date
      20120531-20120603
  • [Presentation] HLA 多型に基づく、がん免疫療法 ・個別化医療の実践2011

    • Author(s)
      西村泰治、中面哲也、冨田雄介、中村祐輔、千住覚
    • Organizer
      第56回日本人類遺伝学会 ・第11回東アジア人類遺伝学会共同大会
    • Place of Presentation
      幕張メッセ(千葉市)
    • Year and Date
      2011-11-10
  • [Presentation] 理想的な癌抗原と ES/iPS 細胞を利用した癌免疫療法の開発2011

    • Author(s)
      西村泰治、中面哲也、冨田雄介、中村祐輔、千住覚
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2011-10-03
  • [Presentation] がん免疫療法:基礎から臨床への橋渡し研究2011

    • Author(s)
      西村泰治
    • Organizer
      第32回癌免疫外科研究会
    • Place of Presentation
      和歌山マリーナシティロイヤルパインズホテル(和歌山市)
    • Year and Date
      2011-05-19
  • [Remarks]

    • URL

      http://www.immgenet.jp/

URL: 

Published: 2014-09-25  

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