| Project/Area Number |
11694301
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
SATO Noriyuki Sapporo Medical University School of Medicine, Professor, 医学部, 教授 (50158937)
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| Co-Investigator(Kenkyū-buntansha) |
BOON Thierry ベルギールートビッヒ癌研究所, 所長
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥12,940,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2001: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2000: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | tumor vaccine / CTL / immunotherapy / HLA-A24 / antigenic peptide / hsc73 / molecular chaperone / ER translocation / ヒト癌抗原 / 抗原ペプチド / hsc 70 / 癌抗原遺伝子 / HLA-A31 / HLA-DR8 / 癌抗原 / キラーT細胞 / HLA / αエノラーゼ / リカバリン / CAR / SYT-SSX融合蛋白 |
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| Research Abstract |
Our studies indicated that 1) inhibitors of apoptosis (IAP) protein were expressed preferentially in neoplastic cells but not in normal tissues. Such IAP, particulary, survivin-and livin-derived HLA-A24-restricted peptides could be immunogenic to cancer patients. 2) Recoverin protein that normally expresses in retina was also detected in more than 50 % of cancer cells and cancer tissues. Recoverin-derived HLA-A24-restricted peptide could also specifically induce CTL in the cancer patients of various tissue origins. 3) SYT-SSX chromosomal translocation (X;18) fusion protein was expressed specifically in approximately 95 % of synovial sarcomas. This protein-derived HLA-A24-restricted peptide could induce antigen-specific CTL, and tetramer study suggested that the precursor of these CTL was detected more frequently in patients with lung metastasis of this tumor. These data implied that above peptides may be useful in human cancer immunotherapy.
We also assessed the role of molecular chaperone, hsc73, in the transport of antigenic peptide into the ER. The data indicated that N-terminus-extended peptides that showed high, but not low, affinity to hsc73 could enter into the ER. This observation is important in determining tumor vaccines, because hsc73-binding peptides may be preferentially associated with MHC class I molecules.
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