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Clinical development of cancer gene therapy using viral vectors

Research Project

Project/Area Number 14207047
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  University of Tokyo, Institute of Medical Science, Professor, 医科学研究所, 教授 (70322071)

Co-Investigator(Kenkyū-buntansha) TSUNODA Takuya  University of Tokyo, Institute of Medical Science, Lecturer, 医科学研究所, 講師 (30275359)
TAKAYAMA Takuya  University of Tokyo, Institute of Medical Science, Research Associate, 医科学研究所, 助手 (10332579)
UCHIDA Hiroaki  University of Tokyo, Institute of Medical Science, Research Associate, 医科学研究所, 助手
KITAMURA Yoshihiro  University of Tokyo, Institute of Medical Science, Assistant Professor, 医科学研究所, 助教授 (10202037)
谷 憲三郎  九州大学, 生体防御医学研究所, 教授 (00183864)
市川 直哉  東京大学, 医科学研究所, 教務職員 (60251451)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥45,890,000 (Direct Cost: ¥35,300,000、Indirect Cost: ¥10,590,000)
Fiscal Year 2004: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2003: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2002: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Keywordsgene Therapy / tumor immunology / adenoviral vector / Inteleukin-12 / GMP / translational research / dendritic cells / IL-12 / 樹上細胞 / アデノウィルスベクター
Research Abstract

The final goal of this project is to establish a system in Japanese academia to support early-phase clinical studies of gene therapy. In order to achieve it, we initiated a process to manufacture adenoviral vector carrying Interleukin-12(Ad-IL-12) to be used in cancer immune-gene therapy protocol using dendritic cells(DCs) transduced with IL-12 genes. To facilitate this project, we started, using our unique facility called "Core Facility for Therapeutic Vectors(CFTV)", making our own master cell bank(MCB) and working cell bank(WCB) of producer cells (293 cells) which have qualities required by the Food and Drug Administration(FDA) of the United States. We have carried on our project as initially proposed and successfully established MCB and WCB which are certified as FDA recommended. At the same time, we constructed cosmid DNA which would be used to make Ad-IL-12. We also made Standard Operating Procedures(SOPs) to ensure the quality of the final products. Furthermore, we also studied on the function and manipulation of DCs which are the target of the gene-transduction and the vehicle to be used in our clinical trial, and revealed important information related to the clinical trial. These results suggest that we are now have a viable system which could support gene therapy clinical protocols in Japan.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (36 results)

All 2004 2003 2002 Other

All Journal Article (24 results) Publications (12 results)

  • [Journal Article] Phase I study of autologous tumor vaccines transduced with the GM-CSF gene in four patients with stage IV renal cell cancer in Japan : clinical and immunological findings2004

    • Author(s)
      Tani K, Tahara H, 他35名
    • Journal Title

      Mol Ther. 10

      Pages: 799-816

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Adenovirus-mediated transfer of siRNA against survivin induced apoptosis and attenuated tumor cell growth in vitro and in vivo.2004

    • Author(s)
      Uchida H, Tahara H, 他9名
    • Journal Title

      Mol Ther. 10

      Pages: 162-171

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Generation of Mature Dendritic Cells Fully Capable of T Helper Type 1 Polarization Using OK-432 Combined with Prostaglandin E2.2004

    • Author(s)
      Sato M, Tahara H.他2名
    • Journal Title

      Cancer Science 94

      Pages: 1091-1098

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Phase I study of autologous tumor vaccines transduced with the GM-CSF gene in four patients with stage IV renal cell cancer in Japan : clinical and immunological findings.2004

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

      Mol Ther. 10

      Pages: 799-816

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Adenoyirus-mediated transfer of siRNA against survivin induced appptosis and attenuated tumor cell growth in vitro and in vivo.2004

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

      Mol Ther. 10

      Pages: 162-171

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Phase I study of autologous tumor vaccines transduced with the GM-C SF gene in four patients with stage IV renal cell cancer in Japan : clinical and immunological finding2004

    • Author(s)
      Tani K, Tahara H, 他35名
    • Journal Title

      Mol Ther. 10

      Pages: 799-816

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adenovirus-mediated transfer of siRNA against survivin induced apoptosis and attenuated tumor cell arowth in vitro and in vivo.2004

    • Author(s)
      Uchida H, Tahara H, 他9名
    • Journal Title

      Mol Ther. 10

      Pages: 162-171

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hydrodynamics-based delivery of the viral interleukin-10 gene suppresses experimental crescentic glomerulonephritis in Wistar-Kyoto rats.2003

    • Author(s)
      Higuchi N, Tahara H, 他9名
    • Journal Title

      Gene Ther 10

      Pages: 1297-1310

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dendritic cells stimulated with a bacterial product, OK-432, efficiently induce cytotoxic T lymphocytes specific to tumor rejection peptide.2003

    • Author(s)
      Nakahara S, Tahara H.他3名
    • Journal Title

      Cancer Research 63

      Pages: 4112-4118

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differential effects of IL-12 on the generation of alloreactive CTL mediated by murine and human dendritic cells : a critical role for nitric oxide.2003

    • Author(s)
      Nishioka Y, Tahara H.他5名
    • Journal Title

      J Leukoc Biol 73

      Pages: 621-629

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Interleukin-17 promotes angiogenesis and tumor growth.2003

    • Author(s)
      Numasaki M, Tahara H.他7名
    • Journal Title

      Blood 101

      Pages: 2620-2627

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] NK but not NKT cells play a necessary role to promote an innate antitumor response induced by IL-18.2003

    • Author(s)
      Hashimoto W, Tahara H.他5名
    • Journal Title

      Int J Cancer 103

      Pages: 508-513

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Generation of Mature Dendritic Cells Fully Capable of T Helper Type 1 Polarization Using OK-432 Combined with Prostaglandin E2.2003

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

      Cancer Science 94

      Pages: 1091-1098

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hydrodynamics-based delivery of the viral interleukin-10 genesuppressesexperimental crescentic glomerulonephritis in Wistar-Kyoto rats.2003

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

      Gene Ther. 10

      Pages: 1297-1310

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Dendritic cells stimulated with a bacterial product, OK-432,efficiently induce cytotoxic T lymphocytes specific to tumor rejection peptide.2003

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

      Cancer Research 63

      Pages: 4112-4118

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Differential effects of IL-12 on the generation of alloreactive CTL mediated by murine and human dendritic cells : a critical role for nitric oxide.2003

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

      J Leukoc Biol 73

      Pages: 621-629

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Interleukin-17 promotes angiogenesis and tumor growth.2003

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

      Blood 101

      Pages: 2620-2627

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] NK but not NKT cells play a necessary role to promote an innate antitumor response induced by IL-18.2003

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

      Int J Cancer 103

      Pages: 508-513

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Therapeutic and specific antitumor immunity induced by co-administration of immature dendritic cells and adenoviral vector expressing biologically active IL-18.2002

    • Author(s)
      Tanaka F, Tahara H.他3名
    • Journal Title

      Gene Ther 9

      Pages: 1480-1486

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Construction and Analysis of New Vector Systems with Improved Interleukin-18 Secretion in Xenogeneic Human Tumor Model2002

    • Author(s)
      Goto H, Tahara H.他8名
    • Journal Title

      J Immunother 25 Suppl 1

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Retroviral delivery of transforming growth factor-β1 to myeloid dendritic cells ; inhibition of T cell priming ability and influence on allograft survival.2002

    • Author(s)
      Takayama T, Tahara H.他4名
    • Journal Title

      Transplantation 74

      Pages: 112-119

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Therapeutic and specific antitumor immunity induced by co-administration of immature dendritic cells and adenoviral vector expressing biologically active IL-18.2002

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

      Gene Ther 9

      Pages: 1480-1486

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Construction and Analysis of New Vector Systems with Improved Interleukin-18 Secretion in Xenogeneic Human Tumor Model2002

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

      J Immunother 25 Suppl 1

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Retroviral delivery of transforming growth factor-β 1 to myeloid dendritic cells ; inhibition of T cell priming ability and influence on allograft survival.2002

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

      Transplantation 74

      Pages: 112-119

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Hashimoto W, Tanaka F, Robbins PD, Taniguch M, Okamura H, Lotze MT, Tahara H: "NK but not NKT cells play a necessary role to promote an innate antitumor response induced by IL-18"Int J Cancer. 103. 508-513 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Numasaki M, Fukushi JI, Ono M, Narula SK, Zavodny PJ, Kudo T, Robbins PD, Tahara H, Lotze MT: "Interleukin-17 promotes angiogenesis and tumor growth."Blood. 101. 2620-2627 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishioka Y, Wen H, Mitani K, Robbins PD, Lotze MT, Sone S, Tahara H.: "Differential effects of IL-12 on the generation of alloreactive CTL mediated by murine and human dendritic cells : a critical role for nitric oxide."J Leukoc Biol. 73. 621-629 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakahara S, Tsunoda T, Baba T, Asabe S, Tahara H: "Dendritic cells stimulated with a bacterial product, OK-432, efficiently induce cytotoxic T lymphocytes specific to tumor rejection peptide."Cancer Research. 63. 4112-4118 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Higuchi N, Maruyama H, Kuroda T, Kameda S, Iino N, Kawachi H, Nishikawa Y, Hanawa H, Tahara H: "Hydrodynamics-based delivery of the viral interleukin-10 gene suppresses experimental crescentic glomerulonephritis Wistar-Kyoto rats."Gene Ther.. 10. 1297-1310 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sato M, Takayama T, Tanaka H, Konishi J, Suzuki T, Kaiga T, Tahara H.: "Generation of Mature Dendritic Cells Ffully Capable of T Helper Type 1 Polarization Using OK-432 Combined with Prostaglandin E2"Cancer Science. 94. 1091-1098 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Adachi O, Nakano A, Sato O, Kawamoto S, Tahara H, Toyoda N, Yamato E, Matsumori A, Tabayashi K, Miyazaki J: "Gene transfer of Fc-fusion cytokine by in vivo electroporation : application to gene therapy for viral myocarditis"Gene Therapy. 9. 577-583 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takayama T, Kaneko K, Morelli AE, Li W, Tahara H, Thomson AW.: "Retroviral delivery of transforming growth factor-□1 to myeloid dendritic cells ; inhibition of T cell priming ability and influence on allograft survival"Transplantation. 74. 112-119 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Goto H, Osaki T, Nishino K, Tachibana I, Takeda Y, Yoneda T, Funakoshi T, Kimura H. Hayashi S, Tahara H: "Construction and Analysis of New Vector Systems with Improved Interleukin-18 Secretion in Xenogeneic Human Tumor Mode"J Immunotherapy. 25 Suppl 1. S35-S41 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tanaka F, Hashimoto W, Robbins PD, Lotze MT, Tahara H: "Therapeutic and specific antitumor immunity induced by co-administration of immature dendritic cells and adenoviral vector expressing biologically active IL-18"Gene Therapy. 9. 1480-1486 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hashimoto W, Tanaka F, Robbins PD, Taniguch M, Okamura H, Lotze MT, Tahara H: "NK but not NKT cells play a necessary role to promote an innate antitumor response induced by IL-18"Int J Cancer. 103. 508-513 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Numasaki M, Fukushi JI, Ono.M, Narula SK, Zavodny PJ, Kudo T, Robbins PD, Tahara H, Lotze MT: "Interleukin-17 promotes angiogenesis and tumor growth"Blood. (In press).

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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