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Induction and characterization of WT1-specific Th1-type CD4(+) T cells to develop WT1 immunotherapy against malignant gliomas.

Research Project

Project/Area Number 19659366
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionHyogo College of Medicine (2008)
Osaka University (2007)

Principal Investigator

IZUMOTO Shuichi  兵庫医科大学, 医学部, 准教授 (40324769)

Co-Investigator(Kenkyū-buntansha) HASHIMOTO Naoya  大阪大学, 医学系研究科, 助教 (90315945)
KISHIMA Haruhiko  大阪大学, 医学系研究科, 助教 (10332743)
TSUBOI Akihiro  大阪大学, 医学系研究科・寄附講座, 准教授 (10372608)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2007: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywords悪性グリオーマ / 膠芽腫 / WT1 / 免疫療法 / ヘルパーT細胞
Outline of Final Research Achievements

WT1ワクチン療法を展開するうえでCD8陽性CTLのみならずWT1腫瘍抗原特異的CD4陽性T細胞(ヘルパーT細胞(Th))の役割を明らかにした。すなわち (1) MHC classⅡ拘束性にマウスWT1特異的CD4陽性T細胞を誘導できるマウスWT1エピトープを同定し、in vivoで、classⅡ拘束性WT1特異CD4陽性T細胞によるWT1特異的CTLの誘導活性化に対する影響、およびそのメカニズム解析を行った。(2)ヒトWT1_<332>ペプチドにより、HLA-DRB1*0405のタイプのみならずHLADRB1*1501、HLA-DRB1*1502、HLA-DRB1*0901のタイプに対しても特異的CD4陽性T細胞の反応が誘導された。WT1_<332>2ペプチドが“promiscuous”に反応するWT1 特異的ヘルパーエピトープであり、今後HLA-class Ⅰ拘束性のWT1ペプチドと組み合わせて、さまざまなHLA-class ⅡタイプでWT1特異的ヘルパーペプチドとしてのがんワクチン療法の相乗効果が考えられた。

Report

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

    (39 results)

All 2009 2008 2007

All Journal Article (25 results) (of which Peer Reviewed: 24 results) Presentation (13 results) Book (1 results)

  • [Journal Article] Gliomaの免疫療法-WT1ペプチドワクチン療法を中心に2009

    • Author(s)
      泉本修一
    • Journal Title

      脳神経外科速報 19

      Pages: 170-177

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phase II clinical trial of Wilms tumor 1 peptide vaccination for patients with recurrent glioblastoma multiforme.2008

    • Author(s)
      Izumoto S
    • Journal Title

      J Neurosurg 108

      Pages: 963-971

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fractional anisotropy and tumor cell density of the tumor core show positive correlation in diffusion tensor magnetic resonance imaging of malignant brain tumors.2008

    • Author(s)
      Kinoshita M
    • Journal Title

      Neuroimage 43

      Pages: 29-35

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical analysis of adhesion molecules and matrix metalloproteinases in malignant CNS lymphomas : a study comparing primary CNS malignant and CNS intravascular lymphomas.2008

    • Author(s)
      Kinoshita M
    • Journal Title

      Brain Tumor Pathol 25

      Pages: 73-78

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serial volumetric assessment of the natural history and growth pattern of incidentally discovered meningiomas.2008

    • Author(s)
      Hashiba T
    • Journal Title

      J Neurosurg 110

      Pages: 675-684

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A multicenter phase I trial of interferon-beta and temozolomide combination therapy for high-grade gliomas. (INTEGRA Study)2008

    • Author(s)
      Wakabayashi T
    • Journal Title

      Jpn J Clin Oncol 383

      Pages: 715-718

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A WT1 protein-derived, naturally processed 16-mer peptide, WT1 (332), is a promiscuous helper peptide for induction of WT1-specific Th1-type CD4(+) T cells.2008

    • Author(s)
      Fujiki F
    • Journal Title

      Microbiol Immunol 52

      Pages: 591-600

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a WT1 protein-derived peptide, WT1, as a HLA-A 0206-restricted, WT1-specific CTL epitope.2008

    • Author(s)
      Li Z
    • Journal Title

      Microbiol Immunol 52

      Pages: 551-558

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] "Cancer antigen WT1 protein-derived peptide"-based treatment of cancer -toward the further development.2008

    • Author(s)
      Oka Y
    • Journal Title

      Curr Med Chem 15

      Pages: 3052-5061

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] WT1 peptide vaccine for the treatment of cancer.2008

    • Author(s)
      Oka Y
    • Journal Title

      Curr Opin Immunol 20

      Pages: 211-220

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Wilms' tumor gene WT1-shRNA as a potent apoptosis-inducing agent for solid tumors.2008

    • Author(s)
      Tatsumi N
    • Journal Title

      Int J Oncol 32

      Pages: 701-711

    • Related Report
      2008 Annual Research Report 2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] グリオーマに対する最新の免疫療法 ; Current orgqn topis : 脳腫瘍-グリオーマ2008

    • Author(s)
      泉本修一
    • Journal Title

      癌と化学療法 35

      Pages: 926-930

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phase II clinical trial of WT1 (Wilms tumor gene) peptide vaccination for patients with recurrent glioblastoma.2008

    • Author(s)
      Izumoto S
    • Journal Title

      J Neurosurg (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neural stem cell factor inhibits glioma invasion.2008

    • Author(s)
      Fujimoto Y
    • Journal Title

      Neurl Res (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of WTl protein and correlation with cellular proliferation in glial tumors.2007

    • Author(s)
      Hashiba T
    • Journal Title

      Neurol Med Chir (Tokyo) 47

      Pages: 165-170

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced epinephrine reserve in response to insulin-induced hypoglycemia in patients with pituitary adenoma.2007

    • Author(s)
      Morita S
    • Journal Title

      Eur J Endocrinol 157

      Pages: 265-270

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and characterization of a WT1 (Wilms Tumor Gene) protein-derived HLA-DRB1*0405-restricted 16-mer helper peptide that promotes the induction and activation of WT1-specific cytotoxic Tlymphocytes.2007

    • Author(s)
      Fujiki F
    • Journal Title

      J Immunother 30

      Pages: 282-93

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Wilms' tumor gene WT1-GFP knock-in mouse reveals the dynamic regulation of WT1 expression in normal and leukemic hematopoiesis.2007

    • Author(s)
      Hosen N
    • Journal Title

      Leukemia 21

      Pages: 1783-1791

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical and immunologic responses to very low-dose vaccination with WT1 peptide (5 microg/body) in a patient with chronic myelomonocyticleukemia.2007

    • Author(s)
      Kawakami M
    • Journal Title

      Int J Hematol 85

      Pages: 426-429

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] WT1 (Wilms' tumor 1)peptide immunotherapy for renal cell carcinoma.2007

    • Author(s)
      Iiyama T
    • Journal Title

      Microbiol Immunol 51

      Pages: 519-530

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] WT1 peptide cancer vaccine for patients with hematopoietic malignancies and solid cancers.2007

    • Author(s)
      Oka Y
    • Journal Title

      Scienticic World Journal 29

      Pages: 649-665

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Wilms tumor gene WT1 peptide-based immunotherapy induced a minimal response in a patient with advanced therapy-resistant multiple myeloma.2007

    • Author(s)
      Tsuboi A
    • Journal Title

      Int J Hematol 86

      Pages: 414-417

    • NAID

      10019533221

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 悪性グリオーマの標準治療2007

    • Author(s)
      泉本修一
    • Journal Title

      脳神経外科速報 17

      Pages: 66-73

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 悪性グリオーマの標準治療と新しい治療2007

    • Author(s)
      泉本修一
    • Journal Title

      Neuro-oncologyの進歩 26

      Pages: 27-33

    • NAID

      130001933525

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 悪性グリオーマにおけるWT1発現解析に基づいた至適WT1ペプチド免疫療法の検討2007

    • Author(s)
      泉本修一
    • Journal Title

      がん治療のあゆみ 26

      Pages: 1-8

    • Related Report
      2007 Annual Research Report
  • [Presentation] 悪性リンパ腫に対するHD-MTX療法の長期治療成績と問題点-多施設共同臨床研究から2008

    • Author(s)
      泉本修一
    • Organizer
      第26回日本脳腫瘍学会
    • Place of Presentation
      松山
    • Year and Date
      2008-12-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] 再発悪性神経膠腫に対するWT1ペプチドワクチン療法-臨床第2相試験-2008

    • Author(s)
      橋本直哉
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-28
    • Related Report
      2008 Annual Research Report
  • [Presentation] 前頭蓋窩巨大髄膜腫の摘出と前頭葉症候群の改善2008

    • Author(s)
      泉本修一
    • Organizer
      第67回日本脳神経外科学会学術総会
    • Place of Presentation
      盛岡
    • Year and Date
      2008-10-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] 悪性神経膠腫に対するWT1ペプチドワクチン免疫療法の治療効果に影響を及ぼす因子2008

    • Author(s)
      千葉泰良
    • Organizer
      第9回日本分子脳神経外科学会
    • Place of Presentation
      京都
    • Year and Date
      2008-08-30
    • Related Report
      2008 Annual Research Report
  • [Presentation] Outcome and efficacy of reduced dose craniospinal irradiation and high-dose chemotherapy for high-risk medulloblastomas.2008

    • Author(s)
      Kagawa N
    • Organizer
      13th Internastional symposium on pediatric neuro-oncology
    • Place of Presentation
      シカゴ・米国
    • Year and Date
      2008-06-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] 悪性グリオーマの免疫療法これまでの流れと最新の治療2008

    • Author(s)
      泉本修一
    • Organizer
      脳腫瘍レビュー'08
    • Place of Presentation
      東京
    • Year and Date
      2008-06-14
    • Related Report
      2008 Annual Research Report
  • [Presentation] WT1 (Wilms tumor gene) peptide vaccination for patients with recurrent glioblastoma.2008

    • Author(s)
      Izumoto S
    • Organizer
      17th Conference of Brain Tumor Research and Therapy
    • Place of Presentation
      函館・日本
    • Year and Date
      2008-06-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] 悪性神経膠腫におけるWT1タンパクの発現とその免疫応答2007

    • Author(s)
      泉本修一
    • Organizer
      第25回日本脳腫瘍学会
    • Place of Presentation
      東京
    • Year and Date
      2007-12-10
    • Related Report
      2007 Annual Research Report
  • [Presentation] Phase II clinical trial of WT1 (Wilms tumor gene) peptide vaccination for patients withrecurrent glioblastom2007

    • Author(s)
      S Izumoto
    • Organizer
      5th ASIAN SOCIETY FOR NERO-ONCOLOGY
    • Place of Presentation
      イスタンブール・トルコ
    • Year and Date
      2007-11-03
    • Related Report
      2007 Annual Research Report
  • [Presentation] 悪性神経膠腫治療におけるWT1免疫療法の可能性2007

    • Author(s)
      泉本修一
    • Organizer
      第45回日本癌治療学会
    • Place of Presentation
      京都
    • Year and Date
      2007-10-24
    • Related Report
      2007 Annual Research Report
  • [Presentation] Low grade gliomaの長期治療成績と遅発性後遺症からみた治療方針の検討2007

    • Author(s)
      泉本修一
    • Organizer
      第66回日本脳神経外科学会総会
    • Place of Presentation
      東京
    • Year and Date
      2007-10-03
    • Related Report
      2007 Annual Research Report
  • [Presentation] Phase II clinical trial of WT1 (Wilms tumor gene) peptide vaccination for patients with recurrent glioblastom2007

    • Author(s)
      S Izumoto
    • Organizer
      3rd International Conference on WT1 in Human Neoplasia
    • Place of Presentation
      ベルリン・ドイツ
    • Year and Date
      2007-09-20
    • Related Report
      2007 Annual Research Report
  • [Presentation] 悪性神経膠腫に対するWT1免疫応答の検討2007

    • Author(s)
      泉本修一
    • Organizer
      第8回日本分子脳神経外科学会
    • Place of Presentation
      兵庫
    • Year and Date
      2007-09-01
    • Related Report
      2007 Annual Research Report
  • [Book] 脳腫瘍の外科、合併症のない脳腫瘍の治療の外科を目指して2007

    • Author(s)
      泉本修一
    • Publisher
      メディカ出版
    • Related Report
      2007 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-11-18  

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