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Novel combined modality therapy with radiotherapy and immunotherapy for the treatment of cancer

Research Project

Project/Area Number 19390314
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Radiation science
Research InstitutionThe University of Tokyo

Principal Investigator

KAKIMI Kazuhiro  The University of Tokyo, 医学部・附属病院, 特任准教授 (80273358)

Co-Investigator(Kenkyū-buntansha) KURACHI Makoto  東京大学, 医学部, 助教 (00396722)
UEHA Satoshi  東京大学, 医学部, 助教 (00447385)
SHIRAISHI Kenshiro  東京大学, 医学部・附属病院, 助教 (40447404)
TAGO Masao  東京大学, 医学部・附属病院, 講師 (50282520)
井垣 浩  東京大学, 医学部附属病院, 助教 (90361344)
木村 公則  東京大学, 医学部附属病院, 助教 (70397339)
Co-Investigator(Renkei-kenkyūsha) IGAKI Hiroshi  東京大学, 医学部・附属病院, 助教 (90361344)
KIMURA Kiminori  東京大学, 医学部・附属病院, 助教 (70397339)
FURUICHI Yoshihiro  東京医科大学, 医学部, 助教 (70384998)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2008: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2007: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
Keywords放射線治療学 / 免疫 / 免疫細胞治療 / γδT細胞 / がん / がん治療 / 放射線治療 / CTL / MDSC / 臨床研究 / 骨転移
Research Abstract

Radiation Immunology & Immunotherapy の確立を目指して、放射線治療と免疫細胞治療に関する基礎的検討と臨床研究を実施した。担癌マウスモデルを用いて、電子線照射が腫瘍と生体の免疫系に与える効果を検討した。腫瘍を取り巻く微小環境内では、Gr-1^+CD11b^+のmyeloid-derived suppressor cells (MDSC) と呼ばれる骨髄系の細胞が蓄積し、ケモカインによって制御されていることを明らかにした。
ex vivoで大量培養したγδT細胞を、骨転移に対する放射線治療後に投与する臨床研究を実施した。前立腺癌に対する抗アンドロゲン治療を受けている患者では、γδT細胞の培養が困難であったが、治療群では病勢コントロールが得られた症例を認めた。

Report

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

    (54 results)

All 2008 2007 Other

All Journal Article (25 results) (of which Peer Reviewed: 15 results) Presentation (25 results) Remarks (4 results)

  • [Journal Article] Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice.2008

    • Author(s)
      Sawanobori Y, Ueha S, Kurachi M, Shimaoka T, Talmadge JE, Abe J, Shono Y, Kitabatake M, Kakimi K, Mukaida N,Matsushima K.
    • Journal Title

      Blood 111

      Pages: 5457-5466

    • Related Report
      2008 Final Research Report
  • [Journal Article] Zoledronate facilitates large-scale ex vivo expansion of functional gammadelta T cells from cancer patients for use in adoptive immunotherapy.2008

    • Author(s)
      Kondo M, Sakuta K, Noguchi A, Ariyoshi N, Sato K, Sato S, Hosoi A, Nakajima J, Yoshida Y, Shiraishi K, Nakagawa K, Kakimi K.
    • Journal Title

      Cytotherapy 10

      Pages: 842-856

    • Related Report
      2008 Final Research Report
  • [Journal Article] Active specific immunotherapy and cell-transfer therapy for the treatment of non-small cell lung cancer2008

    • Author(s)
      Kakimi K, Nakajima J, Wada H.
    • Journal Title

      Lung Cancer

    • Related Report
      2008 Final Research Report
  • [Journal Article] Dendritic cell vaccine with mRNA targeted to the proteasome by polyubiquitination.2008

    • Author(s)
      Hosoi A, Takeda Y, Sakuta K, Ueha S, Kurachi M, Kimura K, Maekawa R, Kakimi K.
    • Journal Title

      Biochem Biophys Res Commun 371

      Pages: 242-246

    • Related Report
      2008 Final Research Report
  • [Journal Article] Memory Th1 cells augment tumor-specific CTL following transcutaneous peptide immunization.2008

    • Author(s)
      Hosoi A, Takeda Y, Furuichi Y, Kurachi M, Kimura K, Maekawa R, Takatsu K, Kakimi K.
    • Journal Title

      Cancer Res 68

      Pages: 3941-3949

    • Related Report
      2008 Final Research Report
  • [Journal Article] がんと免疫-免疫細胞治療について-2008

    • Author(s)
      垣見和宏
    • Journal Title

      PHYSICIANS' THERAPY MANUAL 6(1)

    • Related Report
      2008 Final Research Report
  • [Journal Article] ポストヒトゲノムのがん免疫細胞治療(今後の展開)2008

    • Author(s)
      作田和子、細井亮宏、吉田幸弘、垣見和宏
    • Journal Title

      侵襲と免疫 Vol.17, No.4

      Pages: 149-154

    • Related Report
      2008 Final Research Report
  • [Journal Article] Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice.2008

    • Author(s)
      Sawanobori Y
    • Journal Title

      Blood 111

      Pages: 5457-5466

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Zoledronate facilitates large-scale exvivo expansion of functional gammadelta T cells from cancer patients for use in a doptive immunotherapy.2008

    • Author(s)
      Kohdo M
    • Journal Title

      Cytotheraby. 10

      Pages: 842-856

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Memory Thl cells augment tumor-specific CTL following transcutaneous peptide immunization.2008

    • Author(s)
      Hosoi A
    • Journal Title

      Cancer Res 68

      Pages: 3941-3949

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Active specific immunotherapy and cell-transfer therapy for the treatment of non-small cell lung cancer.2008

    • Author(s)
      Kakimi K,
    • Journal Title

      Lung Cancer (Epub aheadof print)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dendritic cell vaccine with mRNA targeted to the proteasome by polyubiquitination.2008

    • Author(s)
      Hosoi A
    • Journal Title

      Bidchem Biophys Res Commun 371

      Pages: 242-246

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] がんと免疫-免疫細胞治療について2008

    • Author(s)
      垣見和宏
    • Journal Title

      PHYSICIANS' THERAPY MANUAL 6

    • Related Report
      2008 Annual Research Report
  • [Journal Article] ポストヒトゲノムのがん免疫細胞治療(今後の展開)2008

    • Author(s)
      作田和子
    • Journal Title

      侵襲と免疫 17

      Pages: 149-154

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice2008

    • Author(s)
      Sawanobori Y
    • Journal Title

      Blood Epub(掲載確定)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of CD44 in hepatotoxin-mediated liver injury2008

    • Author(s)
      Kimura K
    • Journal Title

      J Hepatol Epub(掲載確定)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Memory Th1 Cells Augment Tunmor-Specific CTL following Transcutaneous Peptide Immunization2008

    • Author(s)
      Hosoi A
    • Journal Title

      Cancer Research (In press)(掲載確定)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dendhtic cell vaccine with mRNA targeted to the proteasome by polyubiquitination2008

    • Author(s)
      Hosoi A
    • Journal Title

      Biochemical and Biophysical Research Commullications (In press)(掲載確定)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathological changes in the gastroitestinal tract of a heavily radiation-exposed worker at the Tokai-mura criticality accident2008

    • Author(s)
      Igaki H, et. al.
    • Journal Title

      Journal of Radiation Research 49(1)

      Pages: 55-62

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Maintenance of memory CD8+ T cell diversity and proliferative potential by a primary response upon re-challenge.2007

    • Author(s)
      Kurachi M, Kakimi K, Ueha S, Matsushima K.
    • Journal Title

      Int Immunol 19

      Pages: 105-115

    • NAID

      40015794096

    • Related Report
      2008 Final Research Report
  • [Journal Article] Impaired IFN-alpha production and the risk of cancer development2007

    • Author(s)
      Uno K
    • Journal Title

      J Interferon Cytokine Res 12

      Pages: 1013-1017

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Verification of in-treatment tumor position using kiovoltage cone-beam computed tomography:a prehminary study2007

    • Author(s)
      Nakagawa K, Igaki H, et. al.
    • Journal Title

      International Journal of Radiation Oncology Biology Physics 69(4)

      Pages: 970-973

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Free radical scavenger edaravone suppresses x-ray-induced apoptosis through p53 inhibition in MOLT-4 cells2007

    • Author(s)
      Sasano N, Igaki H, et. al.
    • Journal Title

      Journal of Radiation Research 48(6)

      Pages: 495-503

    • NAID

      110006452332

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exceptionally high incidence of symptomatic grade 2-5 radiation pneumonitis after stereotactic radiation therapy for lung tumors2007

    • Author(s)
      Yamashita H, Igaki H, et. al.
    • Journal Title

      Radiation Oncology 2

      Pages: 21-21

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Radiotherapy for lymph node metastases in patients with hepatocellular carcinoma:Retrospective study2007

    • Author(s)
      Yamashita H, Igaki H, et. al.
    • Journal Title

      Journal of Gastroenterology & Hepatology 22(4)

      Pages: 523-527

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] シンポジウム4、生体防御と肺癌、S4-4 自己活性化T細胞γδによる非小細胞性肺癌免疫療法2008

    • Author(s)
      中島淳、垣見和宏, 他
    • Organizer
      第49回日本肺癌学会総会
    • Place of Presentation
      北九州市
    • Year and Date
      2008-11-14
    • Related Report
      2008 Final Research Report
  • [Presentation] シンポジウム4、生体防御と肺癌、S4-4自己活性化T細胞γδによる非小細胞性肺癌免疫療法2008

    • Author(s)
      中島淳
    • Organizer
      第49回日本肺癌学会総会
    • Place of Presentation
      北九州市
    • Year and Date
      2008-11-14
    • Related Report
      2008 Annual Research Report
  • [Presentation] Efficient expansion and activation of tumor-specific CTLs by transcutaneous CTL and Th1 epitope peptide immunization with TLR7 ligand.2008

    • Author(s)
      Kazuhiro Kakimi, Akihiro Hosoi, Yayoi Takeda, Ryuji Maekawa, Kiyoshi Takatsu.
    • Organizer
      AACR Annual meeting San Diego, CA.
    • Place of Presentation
      USA
    • Year and Date
      2008-04-13
    • Related Report
      2008 Final Research Report
  • [Presentation] Efficient expansion and activation of tumor-specific CTLs by transcutaneous CTL and Thl epitope peptide immunization with TLR7 ligand2008

    • Author(s)
      Kazuhiro Kakimi,
    • Organizer
      AACR Annual meeting
    • Place of Presentation
      San Diego, CA. USA.
    • Year and Date
      2008-04-13
    • Related Report
      2008 Annual Research Report
  • [Presentation] がんに対する免疫細胞治療法の開発2008

    • Author(s)
      垣見和宏
    • Organizer
      先端医療開発シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2008-01-22
    • Related Report
      2008 Final Research Report
  • [Presentation] ゾレドロン酸を用いて培養したVγ9Vδ2T 細胞による免疫細胞治療2008

    • Author(s)
      大宮、近藤真、作田和子、野口敦崇、有吉直子、佐藤和聡、佐藤志保、佐藤啓介、細井亮宏、中野由貴子、木村公則、垣見和宏
    • Organizer
      第12回基盤的癌免疫研究会総会
    • Related Report
      2008 Final Research Report
  • [Presentation] ケモカインによるCD11b+Gr-1+Myeloid derivedsuppressor cells の担癌宿主内動態制御2008

    • Author(s)
      上羽悟史、沢登靖史、倉知慎、垣見和宏、松島綱治
    • 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] Primary memory CTL preferentially accumulate in secondary lymphoid organs.2008

    • Author(s)
      Kurachi Makoto, Kakimi Kazuhiro, Ueha Satoshi, Suenaga Fumiko, Abe Jun, Matsushima Koji
    • Organizer
      第38回日本免疫学会総会
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report
  • [Presentation] Chemokinemediated rapid turnover of myeloidsuppressor cells in tumor-bearing mice.2008

    • Author(s)
      Ueha S, Sawanobori Y, Shono Y, Abe J, Kurachi M, ShimaokaT,Kitabatake M, Kakimi K, Matsushima K
    • Organizer
      第38回日本免疫学会総会
    • Place of Presentation
      京都
    • Related Report
      2008 Final Research Report
  • [Presentation] ゾレドロン酸を用いて培養したVγ9Vδ2T細胞による免疫細胞治療2008

    • Author(s)
      近藤真
    • Organizer
      第12回基盤的癌免疫研究会総会
    • Place of Presentation
      大宮市
    • Related Report
      2008 Annual Research Report
  • [Presentation] ケモカインによるCDllb+Gr-1+Myeloid derived suppressor cellsの担癌宿主内動態制御2008

    • Author(s)
      上羽悟史
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋市
    • Related Report
      2008 Annual Research Report
  • [Presentation] Primary memory CTL preferentially accumulate in secondaryly mphoid organs.2008

    • Author(s)
      Kurachi Makoto
    • Organizer
      第38回日本免疫学会総会
    • Place of Presentation
      京都市
    • Related Report
      2008 Annual Research Report
  • [Presentation] Chemokine-mediated rapid turnover of myeloid-supPressor cells in tumor-bearing mice.2008

    • Author(s)
      Ueha S,
    • Organizer
      第38回日本免疫学会総会
    • Place of Presentation
      京都市
    • Related Report
      2008 Annual Research Report
  • [Presentation] 経皮ペプチド免疫法を用いた癌ワクチン治療の開発2007

    • Author(s)
      細井亮宏、垣見和宏
    • Organizer
      第5回難病治療開発研究会
    • Place of Presentation
      東京
    • Year and Date
      2007-12-01
    • Related Report
      2008 Final Research Report
  • [Presentation] 細胞治療の基盤と臨床応用, γδT 細胞を用いた免疫細胞治療の取り組み2007

    • Author(s)
      垣見和宏
    • Organizer
      第55回日本輸血・細胞治療学会総会シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2007-06-01
    • Related Report
      2008 Final Research Report
  • [Presentation] 細胞治療の基盤と臨床応用2007

    • Author(s)
      垣見 和宏
    • Organizer
      第55回日本輸血・細胞治療学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-06-01
    • Related Report
      2007 Annual Research Report
  • [Presentation] TLR7 リガンドとTh エピトープペプチドを用いた経皮ペプチド免疫による腫瘍特異的CTLの誘導2007

    • Author(s)
      細井亮宏、竹田やよい、前川隆司、木村公則、高津聖志、垣見和
    • Organizer
      第11回基盤的癌免疫研究会総会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] ユビキチン配列を付加したmRNA を導入した樹状細胞によるCTL の誘導2007

    • Author(s)
      竹田やよい、細井亮宏、前川隆司、木村公則、垣見和宏
    • Organizer
      第11回基盤的癌免疫研究会総会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] ユビキチン配列を付加したmRNA を導入した樹状細胞によるCTL の誘導DC-based vaccine transfected with mRNAencoding proteosomal targeted tumor-associated antigen2007

    • Author(s)
      竹田やよい、細井亮宏、前川隆司、垣見和宏
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] Efficient Expansion and Activation of Tumor-specific CD8+ T cells by Transcutaneous Peptide Immunization with TLR7 ligand and Th1 Epitope Peptide2007

    • Author(s)
      Hosoi Akihiro, Takeda Yayoi, Maekawa Ryuji, Takatsu Kiyoshi, Kakimi Kazuhiro.
    • Organizer
      第37回日本免疫学会総会・学術集会
    • Related Report
      2008 Final Research Report
  • [Presentation] Maintenance of memory CD8+ T cell Diversity and Proloferation Potential by a Primary Response upon Re-Challenge.2007

    • Author(s)
      Kurachi Makoto, Kakimi Kazuhiro, Ueha Satoshi, Matsushima Kouji
    • Organizer
      第37回日本免疫学会総会・学術集会
    • Related Report
      2008 Final Research Report
  • [Presentation] 東海村臨界事故被曝者の消化管障害の病理学的検討2007

    • Author(s)
      井垣 浩、白石 憲史郎、寺原 敦朗, 他
    • Organizer
      日本放射線腫瘍学会第20回学術大会
    • Place of Presentation
      福岡
    • Related Report
      2007 Annual Research Report
  • [Presentation] ユビキチン配列を付加したmRNAを導入した樹状細胞によるCTLの誘導2007

    • Author(s)
      竹田 やよい
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] 癌治療におけるWOWエマルジョンの免疫賦活剤キャリアーとしての応用2007

    • Author(s)
      柳衛 宏宣
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] Efficient Expansion and Activation of Tumor-specific CD8+ Tcells by Transcutaneous Peptide Immunization with TLR7 ligand and Th1 Epitope Peptide2007

    • Author(s)
      細井 亮宏
    • Organizer
      第37回日本免疫学会総会・学術集会
    • Place of Presentation
      東京
    • Related Report
      2007 Annual Research Report
  • [Remarks] 2007/10/13 患者会支援企画、東京大学医学部附属病院22世紀医療センター がん患者さんのための公開講座&施設見学会

    • Related Report
      2008 Final Research Report
  • [Remarks] がんと免疫、免疫細胞治療について

    • Related Report
      2008 Final Research Report
  • [Remarks] 先端医療開発の現状 免疫細胞治療とトランスレーショナルリサーチ 垣見和宏

    • Related Report
      2008 Final Research Report
  • [Remarks] 2008/9/20 日本経済新聞社主催健康と医療フォーラム2008スペシャルセミナーがんと免疫~免疫細胞治療の最前線~特別講演2 「がんと免疫~免疫細胞治療について~垣見和宏

    • Related Report
      2008 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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