Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2013: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2012: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2011: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
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Outline of Final Research Achievements |
Using a novel synthetic vector of a cationic lipid bound with pH-sensitive liposomes, we transfected cytokine genes into tumor cells to manipulate tumor microenvironment for facilitating dendritic cell (DC) therapy. The efficiency of transfection into the LM8 osteosarcoma growing in syngeneic C3H mice was about 10% by both intratumor (i.t.) and intravenous (i.v.) injection of the vector enclosing GFP-expression plasmid. Therapeutic experiments were performed to inhibit LM8 growth by injection of the interferon (IFN) γ-vector or the CD40L-vector, followed by i.t. injection of the DCs presenting the LM8 antigens. Growth of the tumor was significantly suppressed by the treatment of the IFNγ-plasmid vector and the CD40L-plasmid vector. The CD40L-vector treatment led to significantly improved survival. These results indicate that gene transfection of the cytokine genes manipulate the tumor microenvironment effectively and significantly improve DC-based tumor immunotherapy.
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