| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
We previously identified relatively large numbers of cytotoxic T lymphocyte (CTL)-directed peptides by means of cDNA expression cloning methods with cDNAs of various types of cancer. Some of these peptides have been applied for peptide-based immunotherapy. On the other hand, BCG therapy has been applied for the treatment of bladder cancer, while anti-tumor effect of this non-specific immunotherapy is unsatisfactory. Since tumor-specific CTLs are the most potent effector cells toward cancer cells, CTL-directed cancer vaccine for bladder cancer could be effective therapy. However, information about specific immunotherapy or peptide candidates for bladder cancer has not been available. In this study, we attempted to establish a basis for peptide-based immunotherapy for bladder cancer. First we identified tumor antigens for a panel of bladder cancer cell lines using the RT-PCR method. Next, we determined whether or not tumor antigen-derived peptide candidates could induce peptide-specific
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CTLs from the peripheral blood mononuclear cells of HLA-A24+bladder cancer patients. Three tumor antigens, including EZH 2(polycomb group protein enhancer of zeste homolog2), MRP3 (multidrug resistance-associated protein3), and SART3 (SCC antigen recognized by T cells3), were expressed in three of the bladder cancer cell lines. Six tumor antigen-derived peptide candidates (EZH2 291-299, EZH2 735-743, MRP3 503-511, MRP3 1293-1302, SART3 109-118, and SART3 315-323) were selected. Both the EZH2 and the SART3 were faintly detected in the remaining bladder cancer cell line. The EZH2 291-299 peptide successfully induced peptide-specific CTLs from bladder patients. The cytotoxicity of these CTLs has been under investigation. These findings indicate that three tumor antigens, including EZH2, MRP3, and SART3, are appropriate target molecules for specific immunotherapy for bladder cancer patients, and that the EZH2 291-299 peptide can be applicable for CTL-directed peptide vaccine for HLA-A24+bladder cancer patients. Less
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