| Project/Area Number |
15590789
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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 |
Respiratory organ internal medicine
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
YAMAZAKI Koichi Hokkaido University Hospital, Assistant Professor, 病院, 講師 (20312358)
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| Co-Investigator(Kenkyū-buntansha) |
TAMURA Yasuaki Sapporo Medical College School of Medicine, Instructor, 医学部, 助手 (80322329)
TANI Kenzaburo Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (00183864)
AKITA Hirotoshi Hokkaido University, Gradate School of Medicine, Professor, 大学院・医学研究科, 教授 (70222528)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | heat shock protein / gp96 / immuno-gene therapy / CD8 CTL / tumor rejection |
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| Research Abstract |
Heat shock protein gp96 derived from tumors holds tumor antigen peptides and elicits specific protective immunity against parental tumors through the generation of CD8 CTL independent of MHC restriction. However, the therapeutic effects of tumor-derived gp96 on established tumors have not been promising. The present study analyzes the therapeutic effects on established LLC (Lewis Lung Cancer) tumors transduced with ovalbumine (LLC-OVA) of bone marrow-derived dendritic cells (DC) pulsed with LLC-OVA-derived gp96 in immunocompetent C57BL/6 mice. 1×10^5 of LLC-OVA was subcutaneously injected into right frank in C57BL/6 mice and LLC-OVA-derived gp96, DC or DC pulsed with LLC-OVA-derived gp96 was subcutaneously injected into left frank on day 3,7,10 and 14. Therapy with either LLC-OVA-derived gp96 or DC barely affected established LLC-OVA tumor growth. The antitumor effect was significantly enhanced when DC pulsed with 3μg of LLC-derived gp96 was administered. When DC pulsed with LLC-OVA-derived gp96 was co-incubated with specific T-cell receptor (TCR) transgenic CD8+ cells (OT-1), OVA-specific IFN-γ production was not demonstrated. However, therapy with DC pulsed with LLC-OVA-derived gp96 induced slight increase in the numbers of OVA-tetramer positive CD8 T cells in the regional lymph nodes, which revealed that antitumor effect was induced partly by OVA peptides. Conforcal laser microscope showed that gp96 was taken up by DC, entered endosome and transfered their peptides to MHC class I molecules in the endosome. Our data suggest that therapy with DC pursed with tumor-derived gp96 may be useful as potent anti-tumor vaccines.
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