2002 Fiscal Year Final Research Report Summary
Development of gene therapy using chemokine that regulates the mobilization of dendritic cells in situ
| Project/Area Number |
13671220
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAKAYAMA Takuya Institute of Medical Science, The University of Tokyo, Research Associate, 医科学研究所, 助手 (10332579)
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| 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)
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| Project Period (FY) |
2001 – 2002
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| Keywords | dendritic cell / Flt3L / in vivo electroporation / chemokine / SLC |
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| 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)
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