| Project/Area Number |
18591434
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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 | Japanese Foundation For Cancer Research |
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Principal Investigator |
TAKUYA Takayama Japanese Foundation For Cancer Research, Cancer Institute, Division of Cancer Genome Research, Staff Scientist (10332579)
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| Co-Investigator(Kenkyū-buntansha) |
TAHARA Hideaki The University of Tokyo, Institute of Medical Science, Department of Surgery and Bioengineering, Professor (70322071)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,820,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | dendritic cell / IL-18 / FIt3L / SLC / CCL21 |
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| Research Abstract |
1, Combined mobilization and stimulation of tumor-infiltrating dendritic cells and natural killer cells with F1t3 ligand and IL-18 in vivo induces systemic anti-tumor immunity
We focused on the modulation of DCs in tumor microenvironment using F1t3 ligand (F1t3L) combined with IL-18. Tumor-inoculated mice were treated with in vivo electroporation (WE) of expression plasmids carrying cDNA of F1t3L. As combination therapy, mice in the other group were treated with intra-tumoral injection of adenoviral vector carrying IL-18 gene (Ad.IL-18). Significant anti-tumor effect was observed in mice treated with Ad.IL-18 alone when compared with that of control. In un-injected distant tumor, significant anti-tumor responses were observed only in the mice treated with combination therapy. Lymphoid cells in lymph nodes with combination therapy showed significant cytolytic activity against inoculated tumor cells and YAC-1 cells when compared with the ones in other groups. Tumor-infiltrating DCs with combination therapy showed higher CD86 expression and more potent allogeneic T cell stimulatory capacity. These results may suggest that local expression of IL-18 combined with in vivo DC mobilization with F1t3L is clinically applicable as a new strategy of DC immunotherapy. (Submitted for publication)
2, The roles of CC-chemokine ligand 21 on T cell mediated anti-tumor immunity
In order to examine the underlying mechanism of CCL 21 on T cell mediated anti-tumor immunity, we developed an experimental approach of in vitro analysis of CCL 21. This in vitro analysis consisted of mature DCs and naive T cells purified from splenocytes which should express CCR7, and irradiated tumor cells in the presence or absence of recombinant CCL21 protein. CCL21 induced IFN-□ production from naive T cells and this effect needed the direct cell contact between DCs and T cells, and promoted the generation of tumor-specific CTLs.
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