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Preclinical Development of Cellular Gene therapy using Viral Vector

Research Project

Project/Area Number 21249069
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionThe University of Tokyo

Principal Investigator

TAHARA Hideaki  東京大学, 医科学研究所, 教授 (70322071)

Co-Investigator(Kenkyū-buntansha) ITO Akihiko  東京大学, 医科学研究所, 講師 (90241984)
KANAMOTO Akira  東京大学, 医科学研究所, 助教 (10386021)
SATO Marimo  東京大学, 医科学研究所, 助教 (50401253)
地主 将久  北海道大学, 遺伝子病制御研究所, 准教授 (40318085)
Co-Investigator(Renkei-kenkyūsha) JIMUSHI Masahisa  北海道大学, 遺伝子病制御研究所, 准教授 (40318085)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥46,930,000 (Direct Cost: ¥36,100,000、Indirect Cost: ¥10,830,000)
Fiscal Year 2011: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Fiscal Year 2010: ¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Fiscal Year 2009: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Keywords実験外科学 / 腫瘍免疫 / 細胞療法 / 遺伝子治療 / 臨床研究 / ウイルスベクター / ウィルスベクター
Research Abstract

In order to develop cellular-gene therapy against cancer, we have successfully produced cGMP-grade adeniviral vector expressing IL-12. We also performed preclinical safety examination for clinical trials using dendritic cells engineered to produce IL-12 at a high level. Furthermore, we have found the blockade of MFG-E8, an opsonin for phagocytosis, could enhance immune response against cancer cells as a basic research. These results, including generation of clinical grade vector, preclinical safety testing, and basic research to further enhance systemic immune responses, enables the development of novel approach to treat cancer.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (42 results)

All 2012 2011 2010 2009

All Journal Article (20 results) (of which Peer Reviewed: 18 results) Presentation (22 results)

  • [Journal Article] Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors2012

    • Author(s)
      H.Shime
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 109 Issue: 6 Pages: 2066-2071

    • DOI

      10.1073/pnas.1113099109

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of HSV infection through soluble adapter-mediated virus bridging to the EGF receptor2011

    • Author(s)
      Nakano K, Kobayashi M, Nakamura K, Nakanishi T, Asano R, Kumagai I, Tahara H, Kuwano M, Cohene JB, Glorioso JC.
    • Journal Title

      Virology

      Volume: 413巻 Issue: 1 Pages: 2-18

    • DOI

      10.1016/j.virol.2011.02.014

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Medullary interplay for central tolerance2011

    • Author(s)
      Takahama Y
    • Journal Title

      Blood

      Volume: 118 Issue: 9 Pages: 2380-2381

    • DOI

      10.1182/blood-2010-07-293860

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA regulation of vaccinia virus for enhanced oncolytic activity and reduced pathogenicity in oncolytic virotherapy2011

    • Author(s)
      Hikichi M, Kidokoro M, Haraguchi T, Iba H, Shida H, Tahara H & Nakamura T.
    • Journal Title

      Molecular Therapy

      Volume: 19巻 Issue: 6 Pages: 1107-15

    • DOI

      10.1038/mt.2011.36

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells2011

    • Author(s)
      Jinushi M, Chiba S, Yoshiyama H, Masutomi K, Kinoshita I, Dosaka-Akita H, Yagita H, Takaoka A, Tahara H.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 108巻 Issue: 30 Pages: 12425-30

    • DOI

      10.1073/pnas.1106645108

    • NAID

      10030575946

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Early activation and interferon-Y production of tumor-infiltrating mature CD27 high natural killer cells2011

    • Author(s)
      Y.Hayakawa
    • Journal Title

      Cancer Sci

      Volume: 102 Issue: 11 Pages: 1967-1971

    • DOI

      10.1111/j.1349-7006.2011.02042.x

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Proatherogenic Effect of Interleukin-18 is Exerted with High-fat Diet, but not with Normal Diet in Spontaneously Hyperlipidemic Mice2011

    • Author(s)
      Imai T, Oikawa Y, Shimada A, Oguchi S, Takamiya Y, Katsuki T, Okubo Y, Osaki T, Tahara H, Matsushima Y, Miyazaki J, Itoh H.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 18 Issue: 12 Pages: 1090-1101

    • DOI

      10.5551/jat.7567

    • NAID

      130004845359

    • ISSN
      1340-3478, 1880-3873
    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of HSV infection through soluble adapter-mediated virus bridging to the EGF receptor2011

    • Author(s)
      Nakano K, Kobayashi M, Nakamura K, Nakanishi T, Asano R, Kumagai I, Tahara H, Kuwano M, Cohene JB, Glorioso JC
    • Journal Title

      Virology

      Volume: 413 Pages: 2-18

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proatherogenic effect of interleukin-18 is exerted with high-fat diet, but not with normal diet in spontaneously hyperlipidemic mice2011

    • Author(s)
      Imai T, Oikawa Y, Shimada A, Oguchi S, Takamiya Y, Katsuki T, Okubo Y, Osaki T, Tahara H, Matsushima Y, Miyazaki J, Itoh H
    • Journal Title

      J Atheroscler Throimb

      Volume: 18 Pages: 1090-101

    • NAID

      130004845359

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of HSV infection through soluble adapter-mediated virus bridging to the EGF receptor.2011

    • Author(s)
      Nakano K, Kobayashi M, Nakamura K, Nakanishi T, Asano R, Kumagai I, Tahara H, Kuwano M, Cohene JB, Glorioso JC.
    • Journal Title

      Virology

      Volume: 413 Pages: 2-18

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ex-vivo expanded DC induce donor-specific central and peripheral tolerance and prolong the acceptance of donor skin allografts.2011

    • Author(s)
      Yamano T, Watanabe S, Hasegawa H, Suzuki T, Abe R, Tahara H, Nitta T, Ishimaru N, Sprent J, Kishimoto H.
    • Journal Title

      Blood

      Volume: (in press)(掲載確定)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA regulation of vaccinia virus for enhanced oncolytic activity and reduced pathogenicity in oncolytic virotherapy2011

    • Author(s)
      Hikichi M, Kidokoro M, Haraguchi T, Iba H, Shida H, Tahara H, Nakamura T.
    • Journal Title

      Molecular Therapy

      Volume: (In press)(掲載確定)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phase I clinical trial of the vaccination for the patients with metastatic melanoma using gp100-derived epitope peptide restricted to HLA-A* 24022010

    • Author(s)
      Baba T, Sato-Matsushita M, Kanamoto A, Itoh A, Oyaizu N, Inoue Y, Kawakami Y, Tahara H.
    • Journal Title

      J Translational Medicine

      Volume: 8巻 Issue: 1 Pages: 84-95

    • DOI

      10.1186/1479-5876-8-84

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Phase I clinical trial of the vaccination for the patients with metastatic melanoma using gp100-derived epitope peptide restricted to HLA-A*24022010

    • Author(s)
      Baba T, Sato-Matsushita M, Kanamoto A, Itoh A, Oyaizu N, Inoue Y, Kawakami Y, Tahara H
    • Journal Title

      J Translational Medicine

      Volume: 8 Pages: 84-95

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Milk Fat Globule EGF-8 blockade triggers tumor destruction through coordinated cell-autonomous and immune-mediated mechanisms2009

    • Author(s)
      Jinushi M, Sato M, Kanamoto A, Itoh A, Nagai S, Koyasu S, Dranoff G, and Tahara H.
    • Journal Title

      Journal of Experimental Medicine

      Volume: 100巻 Issue: 6 Pages: 1389-1396

    • DOI

      10.1084/jem.20082614

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cytokine gene-mediated immunotherapy : Current status and future perspectives2009

    • Author(s)
      Jinushi M, Tahara H
    • Journal Title

      Cancer Science

      Volume: 100巻 Issue: 8 Pages: 1389-1396

    • DOI

      10.1111/j.1349-7006.2009.01202.x

    • NAID

      10027192998

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Emerging concepts in biomarker discovery ; The US-Japan workshop on immunological molecular markers in oncology2009

    • Author(s)
      Tahara H, et al
    • Journal Title

      Journal of Translational Medicine

      Volume: 7巻 Issue: 1 Pages: 1389-1396

    • DOI

      10.1186/1479-5876-7-45

    • Related Report
      2011 Final Research Report
  • [Journal Article] Milk Fat Globule EGF-8 blockade triggers tumor destruction through coordinated cell-autonomous and immune-mediated mechanisms.2009

    • Author(s)
      Jinushi M, Sato M, Kanamoto A, Itoh A, Nagai S, Koyasu S, Dranoff G, Tahara H.
    • Journal Title

      Journal of Experimental Medicine 100

      Pages: 1389-1396

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytokine gene-mediated immunotherapy : Current status and future perspectives.2009

    • Author(s)
      Jinushi M, Tahara H
    • Journal Title

      Cancer Science 100

      Pages: 1389-1396

    • NAID

      10027192998

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Emerging concepts in biomarker discovery ; The US-Japan workshop on immunological molecular markers in oncology2009

    • Author(s)
      Tahara H., et al.(56 authors in total)
    • Journal Title

      Journal of Translational Medicine 7

      Pages: 45-69

    • Related Report
      2009 Annual Research Report
  • [Presentation] 癌免疫療法の現状と展望(招待講演)2011

    • Author(s)
      田原秀晃
    • Organizer
      第15回日本がん分子標的治療学会学術集会
    • Place of Presentation
      東京都
    • Year and Date
      2011-06-24
    • Related Report
      2011 Final Research Report
  • [Presentation] 癌免疫療法の現状と展望2011

    • Author(s)
      田原秀晃
    • Organizer
      第15回日本がん分子標的治療学会学術集会
    • Place of Presentation
      ホテル日航東京(招待講演)
    • Year and Date
      2011-06-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] Cancer vaccination using tumor cells in situ as the source of tumor antigens2010

    • Author(s)
      田原秀晃
    • Organizer
      13th Asia Pacific-International Molecular Biology Network(A-IMBN) Symposium(Invited Speaker)
    • Place of Presentation
      Chinese Taipei
    • Year and Date
      2010-11-14
    • Related Report
      2011 Final Research Report
  • [Presentation] Cancer vaccination using tumor cells in situ as the source of tumor antigens2010

    • Author(s)
      田原秀晃
    • Organizer
      13th Asia Pacific-International Molecular Biology Network (A-IMBN) Symposium (Invited Speaker)
    • Place of Presentation
      Chinese Taipei
    • Year and Date
      2010-11-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] Cancer vaccination using tumor cells in situ as the source of tumor antigens2010

    • Author(s)
      Hideaki Tahara
    • Organizer
      日本癌学会学術総会(シンポジウム)
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-22
    • Related Report
      2011 Final Research Report
  • [Presentation] Cancer vaccination using tumor cells in situ as the source of tumor antigens2010

    • Author(s)
      Hideaki Tahara
    • Organizer
      日本癌学会学術総会(シンポジウム)
    • Place of Presentation
      大阪、大阪国際会議場リーガロイヤルホテル大阪
    • Year and Date
      2010-09-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] Translational research of clinical dendritic cell therapy using OK-432 and prostaglandin E2(Phase I study)2010

    • Author(s)
      Sato-Matsushita M, Kanamoto A, Katano H, Itoh A, Tahara H
    • Organizer
      14^th International Congress of Immunology
    • Place of Presentation
      神戸市
    • Year and Date
      2010-08-27
    • Related Report
      2011 Final Research Report
  • [Presentation] Translational research of clinical dendritic cell therapy using OK-432 and prostaglandin E2(Phase I study)2010

    • Author(s)
      Sato-Matsushita M, Kanamoto A, Katano H, Itoh A, Tahara H
    • Organizer
      14^<th> International Congress of Immunology
    • Place of Presentation
      神戸市、神戸ポートピアホテル神戸コンベンションセンター
    • Year and Date
      2010-08-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] 生体内に存在する腫瘍細胞を利用した2010

    • Author(s)
      田原秀晃
    • Organizer
      癌免疫療法の開発日本がん免疫学会(シンポジウム)
    • Place of Presentation
      熊本市
    • Year and Date
      2010-07-23
    • Related Report
      2011 Final Research Report
  • [Presentation] 生体内に存在する腫瘍細胞を利用した癌免疫療法の開発2010

    • Author(s)
      田原秀晃
    • Organizer
      日本がん免疫学会(シンポジウム)
    • Place of Presentation
      熊本市、リバーサイドホテル熊本
    • Year and Date
      2010-07-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] 生体内がんワクチン療法の開発2010

    • Author(s)
      田原秀晃
    • Organizer
      日本頭頸部癌学会(特別講演)
    • Place of Presentation
      東京都
    • Year and Date
      2010-06-10
    • Related Report
      2011 Final Research Report
  • [Presentation] 生体内がんワクチン療法の開発2010

    • Author(s)
      田原秀晃
    • Organizer
      日本頭頸部癌学会
    • Place of Presentation
      ウインクあいち(特別講演)
    • Year and Date
      2010-06-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] Cancer vaccination using tumor cells in situ as the source of tumor antigens2010

    • Author(s)
      Hideaki Tahara
    • Organizer
      Working Group meeting(Invited Speaker)
    • Place of Presentation
      米国NCI(Bethesda, MD)
    • Year and Date
      2010-04-22
    • Related Report
      2011 Final Research Report
  • [Presentation] Cancer vaccination using tumor cells in situ as the source of tumor antigens2010

    • Author(s)
      Hideaki Tahara
    • Organizer
      Vaccine Working Group meeting (Invited Speaker)
    • Place of Presentation
      米国NCI (Bethesda, MD)
    • Year and Date
      2010-04-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] Significant enhancement of antigen-specific antitumor effects of DNA vaccine with systemic administration of interleukin-232010

    • Author(s)
      米山公康、佐藤まりも、田原秀晃
    • Organizer
      日本外科学会学術総会
    • Place of Presentation
      名古屋市
    • Year and Date
      2010-04-09
    • Related Report
      2011 Final Research Report
  • [Presentation] Significant enhancement of antigen-specific antitumor effects of DNA vaccine with systemic administration of interleukin-232010

    • Author(s)
      米山公康、佐藤まりも、田原秀晃
    • Organizer
      日本外科学会学術総会
    • Place of Presentation
      名古屋市、名古屋国際会議場
    • Year and Date
      2010-04-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] Antigen-specific antitumor effects of DNA vaccine are significantly enhanced with systemic administration of interleukin(IL)-232009

    • Author(s)
      米山公康、田原秀晃, 他3名
    • Organizer
      日本免疫学会総会
    • Place of Presentation
      大阪市
    • Year and Date
      2009-12-04
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] Cancer vaccination using tumor cells in situ as the source of tumor antigens2009

    • Author(s)
      田原秀晃
    • Organizer
      日本癌学会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2009-10-03
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] Cancer vaccine against malignant melanoma using monocyte-derived dendritic cells stimulated with OK-432 and PGE22009

    • Author(s)
      佐藤まりも、田原秀晃, 他5名
    • Organizer
      日本癌学会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2009-10-02
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] In situ cancer vaccination with anti-MFG-E8 Ab and chemotherapy against solid and hematological tumors2009

    • Author(s)
      地主将久
    • Organizer
      日本癌学会総会
    • Place of Presentation
      横浜市
    • Year and Date
      2009-10-01
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Presentation] Milk-fat globule-EGF8 released from myeloid cells is a critical mediator to facilitate tumor invasion and metastasis2009

    • Author(s)
      地主将久
    • Organizer
      17th International Symposium on Molecular Cell Biology of Macrophage
    • Place of Presentation
      金沢市
    • Year and Date
      2009-07-03
    • Related Report
      2011 Final Research Report
  • [Presentation] Milk-fat globule-EGF8 released from myeloid cells si a critical mediator to facilitate tumor invasion and metastasis2009

    • Author(s)
      地主将久
    • Organizer
      17th International Symposium on Molecular Cell Biology of Macrophage
    • Place of Presentation
      金沢市
    • Year and Date
      2009-07-03
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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