| Project/Area Number |
12671557
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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 |
Urology
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
TACHIBANA Masaaki Tokyo Medical University, Medicine, Professor, 医学部, 教授 (70129526)
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| Co-Investigator(Kenkyū-buntansha) |
NAMIKI Kazunori Tokyo Medical University, assistant, 医学部, 助手 (40256243)
ITO Takaaki Tokyo Medical University, assistant professor, 医学部, 助教授 (90223156)
小津 兆一郎 慶應義塾大学, 医学部, 助手 (90296674)
堀口 裕 慶應義塾大学, 医学部, 助手 (60229234)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | Prostate cancer / PSMA / HLA-A24 / epitope peptide / dendritic cells / treatment / ワクチン治療 / 免疫細胞治療 |
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| Research Abstract |
Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein predominantly expressed in prostate cancer, is an attractive target for tumor-specific immunotherapy. To identify HLA-A24-restricted epitope peptides from PSMA for further application of the dendritic cells (DC)-based immunotherapy targeting prosate cancer, we have screened several PSMA-encoded HLA-A24 binding peptides for their capabilities to elicit specific antitumor cytotoxic T-lymphocytes (CTL) response in vitro. A total of 9 peptides were studied if they could elicit CTL responses by primary in vitro immunization of CD8+ T cells using preptide-pusled autologous DC derived from peripheral blood mononuclear cells of HLA-A24+Healthy donor as antigen-presenting cells. Two peptides, Lysdpadyf and NYATEDFF, were indentified to be able to elicit CLT lines that lysed HLA-A24+target cells pulsed with each peptides. The antigen specificity of the CTL lines was confirmed utilizing several tumor cell lines as target cells, which were gen I and anti-CD8 monoclonal antibdies (mABs) bur not by anti-MHC class II and anti-CD4mABs. The identification of these novel HLA-A-24-restricted PSMA epitope peptides would provide us the opportunity to further evaluate the clinical feasibility of DC-based immunotherapeutic strategy against hormone-refractory prostate cancers.
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