Development of allogeneic dendriticcell /tumor cell fusion hybrids vaccine based on MHC classI restriction
| Project/Area Number |
16591316
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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 |
Digestive surgery
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| Research Institution | Kobe University |
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Principal Investigator |
KAMIGAKI Takashi Kobe University, Hospital, Surgery, Associate Professor (20372641)
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| Co-Investigator(Kenkyū-buntansha) |
TAKASE Shiro Kobe University Hospital, Surgery, Associate Professor (00379405)
IWATANI Yoshiteru Kobe University Hospital, Surgery, Medical Staff (00457079)
NAKAMURA Tetsu Kobe University Hospital, Surgary, Medical Staff (10403247)
KURODA Yoshikazu Kobe University, Graduate school of Medical Science Surgery, Professor (70178143)
味木 徹夫 神戸大学, 大学院医学系研究科, 助手 (80379403)
川崎 健太郎 神戸大学, 医学部附属病院, 助手 (90379404)
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| Project Period (FY) |
2004 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,850,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | colorectal cancer / dendritic cell / MHC / CTL / VK / cancer vaccine / DC / TC fusion hybrids / tumor immunoloey / アロ樹状細胞 / 腫瘍細胞・樹状細胞融合 / 抗CD25抗体 / 腫瘍予防モデル / 制御性Tリンパ球 / 細胞傷害性Tリンパ球 / CT26大腸癌細胞株 / 肺転移 / CT26大腸癌細胞 / gp70 env MuLV / Pentamer / pentamer |
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| Research Abstract |
1.Comparative analysis of antigen loading methods for denderitic cell-based vaccine for murine colon cancer models
1) Dentdritic cell / tumor cell (DC/ TC) fusion hybrids elicited the most effective anti-turnor response, as compared to other antigen-loading vaccines in animal models.
2) DC/TC fusion hybrids induced higher cytotoxic T lymphocyte (CTL) activity than other vaccines and the production of IFN-γ polarized to the Th1 cytokine responses.
2. Correlation between expression of MHC class I and that of antigen presenting machineries in gastrointestinal cancers
1) It was shown that β2-microglobulin and LMP-2 are important for the expression of MHC class I in pancreas, biliary tract, and colon cancer cell lines.
2) Transfection of the wild-type β2-microglobulin gene restored MHC class I antigen expression on the cell surface for the colon cancer cell line, which showed no MHC class I expression and lack of protein expression for β2-microglobulin.
3. Development of allogeneic DC/ TC fusion hybrids vaccine for colon cancer
1) Allogeneic DC/TC fusion hybrids induced greater anti-tumor efficacy compared to syngeneic fuson hybrids in murine colon cancer models.
2) Allogeneic DC/TC fusion hybrids elicited stronger CTL and NK activity than syngeneic DC/TC hybrids. Because it was found that allogeneic DC/TC hybrids induced the higher production of IFN-γ and the higher ratio of the Th1 to Th2 cytokine.
3) Additionally, DC/TC fusion hybrids vaccine induced CTLs specific to both endogenous and exogenous antigens in animal models.
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Report
(5 results)
Research Products
(30 results)
