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The establishment and clinical application of new immunotherapy for gynecologic cancers by using the activation of self-tolerance

Research Project

Project/Area Number 18209052
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKyoto University

Principal Investigator

TAKAKURA Kenji (2007-2008)  Kyoto University, 医学研究科, 非常勤講師 (10221350)

藤井 信吾 (2006)  京都大学, 医学研究科, 教授 (30135579)

Co-Investigator(Kenkyū-buntansha) MANDAI Masaki  京都大学, 医学研究科, 講師 (80283597)
YAGI Haruhiko  京都大学, 医学研究科, 助教 (70402857)
SAKAGUCHI Shimon  京都大学, 再生医科学研究所, 教授 (30280770)
OKAZAKI Taku  京都大学, 医学研究科, 准教授 (00362468)
高倉 賢二  京都大学, 医学研究科, 助教授 (10221350)
Co-Investigator(Renkei-kenkyūsha) OKAZAKI TAKU  徳島大学, 医学部, 教授 (00362468)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥50,310,000 (Direct Cost: ¥38,700,000、Indirect Cost: ¥11,610,000)
Fiscal Year 2008: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2007: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2006: ¥33,930,000 (Direct Cost: ¥26,100,000、Indirect Cost: ¥7,830,000)
Keywords婦人科腫瘍 / 腫瘍免疫 / PD-1 / 制御性T細胞 / 免疫逃避機構 / BMP / NK細胞 / 免疫回避機構 / 婦人科悪性腫瘍 / PD-L1
Research Abstract

婦人科悪性腫瘍の多くは初期治療反応性は良いが、長期的予後は良くない。このため腫瘍免疫療法等の新しい治療法の開発が必要である。腫瘍は本来不可欠な自己寛容維持機構をうまく利用することで免疫系の攻撃から逃れていると考えられ、本研究で我々は、自己寛容維持のメカニズムを逆に利用して、これを一過性に抑制し、ある程度の自己免疫状態を惹起することによって強力な自己免疫を得るという新しい治療法を婦人科悪性腫瘍に対して導入する基礎的検討を行なうことができた。

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (30 results)

All 2009 2008 2007 2006

All Journal Article (15 results) (of which Peer Reviewed: 8 results) Presentation (15 results)

  • [Journal Article] Clinical significance of the NKG2D ligands, MICA/B and ULBP2 in ovarian cancer2009

    • Author(s)
      Li K, Mandai M, Hamanishi J, Kenji Takakura et.al.
    • Journal Title

      Cancer Immunol Immunother 58

      Pages: 649-649

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Classification using hierarchical clustering of tumor-infiltrating immune cells identifies poor prognostic ovarian cancers with high levels of COX expression2009

    • Author(s)
      Liu M, Matsumura N, Mandai M, Kenji Takakura et.al.
    • Journal Title

      Modern Pathology 22

      Pages: 373-378

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical significance of the NKG2D ligands, MICA/B and ULBP2 in ovarian cancer.2009

    • Author(s)
      Li K, Mandai M, Hamanishi J, et al.
    • Journal Title

      Cancer Immunol Immunother. 58

      Pages: 641-652

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Classification using hierarchical clustering of tumor-infiltrating immune cells identifies poor prognostic ovarian cancers with high levels of COX expression.2009

    • Author(s)
      Liu M, Matsumura N, Mandai M, et al.
    • Journal Title

      Mod Pathol. 22

      Pages: 373-384

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunostimulatory effect of Fms-like tyrosine kinase 3 ligand on peripheral monocyte-derived dendritic cells2008

    • Author(s)
      Baba T, Mori S, Matsumura N, Kariya M, Murphy SK, Kondoh E, Kusakari T, Kuroda H, Mandai M, Higuchi T, Takakura K, Fukuda MN, Fujii S.
    • Journal Title

      Oncol Rep. 19

      Pages: 19-19

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer2007

    • Author(s)
      Hamanishi J, Mandai M, Iwasaki M, Okazaki T, Tanaka Y, Yamaguchi K, Higuchi T, Yagi H, Takakura K, Minato N, Honjo T, Fujii S
    • Journal Title

      Proc Natl Acad Sci USA 104(9)

      Pages: 3360-5

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] 臨床医学の展望2007婦人科学」婦人科腫瘍と免疫2007

    • Author(s)
      濱西潤三、藤井信吾
    • Journal Title

      日本医事新報 No.4320

      Pages: 87-88

    • Related Report
      2008 Final Research Report
  • [Journal Article] Trophinin is a potent prognostic marker of ovarian cancer involved in platinum sensitivity.2007

    • Author(s)
      Baba T, Mori S, Matsumura N, Kariya M, Murphy SK, Kondoh E, Kusakari T, Kuroda H, Mandai M, Higuchi T, Takakura K, Fukuda MN, Fujii S.
    • Journal Title

      Biochem Biophys Res Commun. 360

      Pages: 363-9

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuropilin-1 promotes unlimited growth of ovarian cancer by evading contact inhibition.2007

    • Author(s)
      Baba T, Kariya M, Higuchi T, Mandai M, Matsumura N, Kondoh E, Miyanishi M, Fukuhara K, Takakura K, Fujii S
    • Journal Title

      Gynecol Oncol 105

      Pages: 703-11

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer.2007

    • Author(s)
      Hamanishi J, Mandai M, Iwasaki M, Okazaki T, (5), Minato N, Honjo T, Fujii S.
    • Journal Title

      Proc Natl Acad Sci U S A. 104(9)

      Pages: 3360-3365

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Immortalized ovarian surface epithelial cells acquire tumorigenicity by Acrogranin gene overexpression.2007

    • Author(s)
      Miyanishi M, Mandai M, Matsumura N, (3), Takakura K, Fujii S.
    • Journal Title

      Oncol Rep. 17(2)

      Pages: 329-333

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Foxp3 controls regulatory T-cell function by interacting with AMLl/Runxl.2007

    • Author(s)
      Ono M, Yaguchi H, Ohkura N, (4), Tsukada T, Sakaguchi S.
    • Journal Title

      Nature 446 (7136)

      Pages: 685-689

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Foxp3 and Aire in thymus-generated T (reg) cells : a link in self-tolerance.2007

    • Author(s)
      Nomura T, Sakaguchi S.
    • Journal Title

      Nat Immunol. 8(4)

      Pages: 333-334

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The PD-1-PD-L pathway in immunological tolerance.2007

    • Author(s)
      Okazaki T, Honjo T.
    • Journal Title

      Trends Immunol. 27(4)

      Pages: 195-201

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Oncogenic property of acrogranin in human uterine leiomyosarcoma : direct evidence of genetic contribution in in vivo tumorigenesis.2006

    • Author(s)
      Matsumura N, Mandai M, Miyanishi M, (4), Takakura K, Fujii S.
    • Journal Title

      Clin Cancer Res. 12(5)

      Pages: 1402-1411

    • Related Report
      2006 Annual Research Report
  • [Presentation] 卵巣癌腹膜播種の新生血管を標的として、ケモカイン遺伝子(CCL19)導入胚性血管内皮前駆細胞を用いて局所免疫賦活を目指した新規免疫療法開発の基礎的検討2009

    • Author(s)
      濱西潤三、万代昌紀、樋口壽宏、山口建高倉賢二、藤井信吾、小西郁生
    • Organizer
      第61回日本産科婦人科学会学術講演会
    • Place of Presentation
      京都
    • Year and Date
      2009-04-05
    • Related Report
      2008 Final Research Report
  • [Presentation] Activated local immunity by chemokine CCL19-transduced embryonic endothelial progenitor cells suppresses lung metastasis of murine ovarian cancer2009

    • Author(s)
      Hamanishi J, Mandai M, Higuchi T, Yamaguchi K, Takakura K, Fujii S, Konishi I
    • Organizer
      40th Annual Meeting of Women's Cancer
    • Place of Presentation
      San Antonio, Texas
    • Year and Date
      2009-02-06
    • Related Report
      2008 Final Research Report
  • [Presentation] 卵巣癌の新生血管を標的としてケモカイン遺伝子(CCL19)導入血管内皮前駆細胞を用いた局所免疫賦活療法2008

    • Author(s)
      濱西潤三、万代昌紀、樋口壽宏、山口建、高倉賢二、藤井信吾、小西郁生
    • Organizer
      第44回日本婦人科腫瘍学会学術講演会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-07-19
    • Related Report
      2008 Final Research Report
  • [Presentation] 卵巣癌におけるNK細胞活性化受容体のリガンド発現とその意義2008

    • Author(s)
      Li K., Mandai M, et al.
    • Organizer
      日本婦人科腫瘍学会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-07-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] 卵巣癌におけるNK細胞活性化受容体のリガンド発現とその意義2008

    • Author(s)
      濱西潤三、李奎、万代昌紀、樋口壽宏、山口建、高倉賢二、藤井信吾
    • Organizer
      第60回日本産科婦人科学会学術講演会
    • Place of Presentation
      横浜
    • Year and Date
      2008-04-13
    • Related Report
      2008 Final Research Report
  • [Presentation] Activated local immunity by CCL19- transduced endothelial progenitor cells suppresses lung metastasis2008

    • Author(s)
      Hamanishi J, Mandai M, Higuchi T, Yamaguchi K, Takakura K, Fujii S, Konishi I
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Final Research Report
  • [Presentation] 卵巣癌の新生血管での局所免疫賦活を目指した胚性血管内皮前駆細胞によるターゲティング療法2007

    • Author(s)
      濱西潤三、万代昌紀、樋口壽宏、山口建、高倉賢二、藤井信吾
    • Organizer
      第12回生殖医療フォーラム
    • Place of Presentation
      奈良
    • Year and Date
      2007-06-13
    • Related Report
      2008 Final Research Report
  • [Presentation] Programmed cell death-1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are independent parognostic factors2007

    • Author(s)
      万代昌紀
    • Organizer
      COE international symposium 2007
    • Place of Presentation
      京都
    • Year and Date
      2007-06-02
    • Related Report
      2007 Annual Research Report
  • [Presentation] 卵巣癌の新生血管での局所免疫賦活を目指した胚性血管内皮前駆細胞によるターゲティング療法2007

    • Author(s)
      濱西潤三、万代昌紀、樋口壽宏、山口建、高倉賢二、藤井信吾
    • Organizer
      第59回日本産科婦人科学会学術講演会
    • Place of Presentation
      京都
    • Year and Date
      2007-04-17
    • Related Report
      2008 Final Research Report
  • [Presentation] 免疫抑制性補助シグナル分子PD-L1発現は卵巣癌の予後と相関する2007

    • Author(s)
      濱西潤三、万代昌紀、樋口壽宏、山口建、高倉賢二、藤井信吾
    • Organizer
      第59回日本産科婦人科学会学術講演会
    • Place of Presentation
      京都
    • Year and Date
      2007-04-17
    • Related Report
      2008 Final Research Report
  • [Presentation] 卵巣癌における免疫抑制性補助シグナル分子PD-L1発現と予後との相関2006

    • Author(s)
      濱西潤三、万代昌紀、樋口壽宏、刈谷方俊、高倉賢二、藤井信吾
    • Organizer
      第40回日本婦人科腫瘍学会学術講演会シンポジウム
    • Place of Presentation
      岐阜
    • Year and Date
      2006-07-21
    • Related Report
      2008 Final Research Report
  • [Presentation] 婦人科癌再発症例に対する拡大手術の試み~難治性子宮頚癌再発症例に対する骨盤半截術の経験~2006

    • Author(s)
      濱西潤三、樋口壽宏、福原健、由良茂夫、万代昌紀、刈谷方俊、高倉賢二、藤井信吾
    • Organizer
      第58回日本産科婦人科学会学術講演会
    • Place of Presentation
      横浜
    • Year and Date
      2006-04-25
    • Related Report
      2008 Final Research Report
  • [Presentation] 卵巣癌におけるProgrammed cell death-Ligand 1(PD-L1)蛋白の発現2006

    • Author(s)
      濱西潤三、万代昌紀、岡崎拓、本庶佑、藤井信吾
    • Organizer
      21世紀COEコロキウム京都大学大学院医学研究科「病態解明における基礎・臨床連携の進捗」
    • Place of Presentation
      京都
    • Year and Date
      2006-01-21
    • Related Report
      2008 Final Research Report
  • [Presentation] Prognostic significance of programmed cell death-1 ligand and tumor- infiltrating CD8+ lymphocytes in human ovarian cancer2006

    • Author(s)
      Junzo Hamanishi, Masaki Mandai, Taku Okazaki, Tasuku Honjo Shingo Fujii
    • Organizer
      21century COE Colloquium on Immunology 2006 4th
    • Place of Presentation
      Kyoto
    • Related Report
      2008 Final Research Report
  • [Presentation] Targeting of tumor vessels and activation of local tumor immunity using embryonic endothelial progenitor cells (eEPCs) lead to tumor suppression in lung metastatic model of ovarian cancer2006

    • Author(s)
      Junzo Hamanishi, Masaki Mandai, Shingo Fujii
    • Organizer
      21century COE Colloquium on Immunology 2006 4th
    • Place of Presentation
      Kyot
    • Related Report
      2008 Final Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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