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Development of gene therapy using chemokine that regulates the mobilization of dendritic cells in situ

Research Project

Project/Area Number 13671220
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

TAKAYAMA Takuya  Institute of Medical Science, The University of Tokyo, Research Associate, 医科学研究所, 助手 (10332579)

Co-Investigator(Kenkyū-buntansha) TSUNODA Takuya  Institute of Medical Science, The University of Tokyo, Associate Professor, 医科学研究所, 講師 (30275359)
TAHARA hideaki  Institute of Medical Science, The University of Tokyo, Professor, 医科学研究所, 教授 (70322071)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsdendritic cell / Flt3L / in vivo electroporation / chemokine / SLC / dendritic cell / chemokine / CCR7 / 腫瘍免疫
Research Abstract

1) Retroviral transduction of myeloid DC progenitors to overexpress TGF-beta is associated with marked impairment of their T-cell allostimulatory activity but with only modest prolongation of organ allograft survival. (ref. 1)
2) We have established the genetically modified DC to regulate the immune response. We have also focused on Flt3-Ligand, a recently reported cytokine, is a stimulator for proliferation and differentiation of DC not only in vitro but in vivo. In this study, we evaluated the effects of FH3-Ligand on DC mobilization, proliferation, maturation and immune response using in vivo electroporation (IVE). After Flt3-Ligand trasfection using IVE, significantly high level of FH3-Ligand was detected in the serum during 10days after IVE. The frequency of DC both in spleen and bone marrow significantly was increased after Flt3-Ligand IVE when compared with those of control group. In mouse tumor model, FH3-Ligand IVE induced anti-tumor effect that was associated with proliferation and mobilization of DC. These results implied that Flt3-Ligand gene transfer using IVE could utilize to the clinical application for cancer gene therapy. (ref. 2)
3) Secondary lymphoid-tissue chemokine (SLC), which is a member of CC chemokine, promotes the migration of mature dendritic cell (DC) expressed CCR7. In this study, we are going to examine the efficacy of SLC on DC mobilization in vivo and anti-tumor immunity by SLC gene modified tumor vaccination. (accepted as an oral presentation in The 103rd Annual Congress of Japan Surgical Society)

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [Publications] Takayama T, Kaneko K, Morelli AE, Li W, Tahara H, Thomson AW: "Retroviral delivery of transforming growth factor-beta1 to myeloid dendritic cells : inhibition of T-cell priming ability and influence on allograft survival"Transplantation. 74巻1号. 112-119 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Enomoto K, Takayama T, Shibata M, Fukuzawa M, Tahara H.: "Mobilization and maturation of dendritic cells in vivo using Flt3-Ligand gene transfer with in vivo electroporation"Journal of Nihon University Medical Association. 60. 480-484 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takayama T, Kaneko K, Morelli AE, Li W, Tahara H. Thomson AW.: "Retroviral delivery of transforming growth factor-betal to myeloid dendritic cells : inhibition of T-cell priming ability and influence on allograft survival"Transplantation. 74. 112-119 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Enomoto K, Takayama T, Shibata M, Fukuzawa M, Tahara H.: "Mobilization and maturation of dendritic cells in vivo using Flt3-Ligand gene transfer with in vivo electroporation"Journal of Nihon University Medical Association. 60. 480-484 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takayama T, Kaneko K, Morelli AE, Li W, Tahara H, Thomson AW: "Retroviral delivery of transforming growth factor-beta1 to myeloid dendritic cells : inhibition of T-cell priming ability and influence on allograft survival"Transplantation. 74巻1号. 112-119 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takayama T, Morelli AE, Onai N, Hirao M, Matsushima K, Tahara H, Thomson AW: "Mammalian and viral IL-10 enhance C-C chemokine receptor 5 but down-regulate C-C chemokine receptor 7 expression by myeloid dendritic cells : impact on chemotactic responses and in vivo homing ability"Journal of Immunology. 166. 136-143 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takayama T, Tahara H, Thomson AW: "Differential effects of myeloid dendritic cells retrovirally transduced to express mammlian or viral IL-10 CTL and NK cell activities and resistance to tumor growth"Transplantation 71:1334-40, 2001. 71. 1334-1340 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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