| Project/Area Number |
09557046
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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 | 展開研究 |
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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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| Co-Investigator(Kenkyū-buntansha) |
SUNAMOTO Junzo Kyoto University, Professor, 大学院, 教授 (80037811)
NAKAMURA Hideo Yokohama Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., Investigator, 横浜研究所, 主任研究員
池田 裕明 三重大学, 医学部・附属病院, 医員
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 1999: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1997: ¥6,100,000 (Direct Cost: ¥6,100,000)
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| Keywords | hydrophobized polysaccharide / pullulan / CTL / tumor antigen / HER2 / adjuvant / tumor rejection antigen / antigen peptide |
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| Research Abstract |
We designed a novel and simple protein delivery system for center immunotherapy : cholesteryl group-bearing polysaccharides, mannan and pullulan (CHM and CHP), complexed with the truncated HER2 protein containing the 147N-terminal amino acids. CHM-HER2 were able to induce CD8ィイD1+ィエD1 CTLs against HER2ィイD1+ィエD1 tumors. These CTLs were KィイD1dィエD1 restricted and recognized specifically HER2p63-71, a part of a truncated HER2 protein used as an immunogen. Mice immunized with CHM-HER2 or CHP-HER2 before tumor challenge, successfully rejected HER2ィイD1+ィエD1 tumors. The complete rejection of tumors implantation. In the effector phase of in vino tumor rejection, CDィイD1+ィエD1 T cells played a major role.
Mice were immunized with CHP-HER2 and proliferative response of CD8ィイD1+ィエD1 T cells was examined by stimulating them with DCs pretreated with CHP-HER2, which shows that DCs can incorporate CHP-HER2 efficiently and present cognate peptides to CD8ィイD1+ィエD1 T cells after appropriate processing. We further examined whether DCs treated ex vivo with CHP-HER2 could be used as vaccine against HER2 expressing tumor cells. HER2 expressing tumor cells were inoculated into mice, and 10 days later, vaccinated with CHP-HER2 pretreated with CHP-HER2 was started. Only in the group of mice vaccinated with CHP-HER2 pretreated DCs, complete eradication of tumor was observed. Human bone marrow-derived dendritic cells cocultured with CHP-HER2 became susceptible to a HLA-A24 restricted CTL clone specific for HER2p63-71 and also induced its proliferation.
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