| Project/Area Number |
12470114
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
|
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| Research Institution | Mie University |
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Principal Investigator |
SHIKU Hiroshi Mie University, Faculty of Medicine, Professor, 医学部, 教授 (80154194)
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| Project Period (FY) |
2000 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2002: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2001: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2000: ¥6,100,000 (Direct Cost: ¥6,100,000)
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| Keywords | HER2 / CTL / helper T cell / antigen peptide / DNA vaccine / anti-tumor immune response / tumor rejection antigen / 原癌遺伝子 / 癌ワクチン / ペプチド |
|---|
| Research Abstract |
We identified a HER2-derived T helper cell (Th) epitope (HER2_<16-30>) and examined the role of Th cell epitope in HER2-specific cytotoxic T lymphocyte (CTL) induction and in vivo tumor eradication with a particular emphasis on the role of tumor cell-derived Th epitopes. Immunization using a mixture of Th epitope HER2_<16-30> and a CTL epitope HER2_<63-71> administered subcutaneously with mGM-CSF induced a much higher level of HER2-specific CTL compared with that of CTL epitope alone. HER2-unrelated OVA-derived Th epitope (OVA_<323-339>) exhibited a similar enhancing effect on p63-specific CTL induction in BALB/c mice. However, only mice immunized with HER2_<16-30> plus HER2_<63-71>, but not with a tumor-unrelated OVA_<323-339> plus HER2_<63-71>, showed in vivo tumor eradication of HER2-expressing syngeneic tumor cells CMS5mHE. This distinction was observed in preventative as well as therapeutic experimental settings. Conversely, both HER2_<16-30> and OVA_<323-339> Th epitopes were equ
… More
ally effective in inducing tumor eradication of CMS5mOVAHE, which expressed HER2 as well as OVA. Our results clearly indicate that CTL and Th peptides of the target tumor cell origin should be used for effective induction of in vivo antitumor immunity.
A variety of tumor-derived antigens have been defined by IgG antibodies in tumor bearer's sera with SEREX, a serological expression cloning method. Majority of them show no structural abnormality and appear to be wild type autoantigens. Coimmunization with DNA encoding these autoantigens and tumor-specific cytotoxic T lymphocytes (CTL) epitopes heightened CD8^+ T cell responses and increased resistance to tumor challenge in a CD4^+ T cell dependent manner. In contrast, immunization with SEREX antigen alone leads to heightened susceptibility to tumor challenge and decreased natural killer T (NKT) responses. This suppressive effect of immunization is mediated by CD4^+ CD25^+ regulatory T cells. We propose that SEREX identifies the pool of autoantigens that maintains and regulates immunological homeostasis via CD4^+ T cells. Less
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