| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
We had cloned 6 cancer antigen genes and those derived 10 epitope peptides recognized by cytotoxic T-lymphocytes in an HLA-restricted manner were identified. Their expression is not restricted in the lung cancers but also found in other adenocarcinomas and squamous cell carcinomas with relatively high level of expression. Therefore we conducted clinical trials, as the translational research, of the personalized peptide vaccines for patients with various cancers including cancers of the lung, colon, stomach, pancreas, prostate, and malignant brain tumors in total 178 cases using these epitope peptides with previously identified peptides. Local inflammation at the injected sites was frequently observed, however, systemic adverse events have not been detected except for fever(grade 2 of CTCAE ver 3)in some cases. These results indicated the safety of the personalized peptide vaccines. Anti-tumor effects of the vaccines were confirmed in patients with glioblastoma maltiforme. In the case of hormone refractory prostate cancers, combination therapy with the vaccines and low dose estramustin phosphate expressed clinical effects. Since some of the vaccine peptides elicited immediate hypersensitivity-like skin reactions in the prevaccination skin tests, precise mechanisms of the reaction was investigated in animal models. The peptide-induced skin reaction was elicited by degranulation of the mast cells with antibody-independent mechanisms. However, this degranulation of the mast cells was not induced systemic anaphylaxis, because of the rapid degradation of the vaccine peptides in the plasma. This phenomenon was unelated to the anti-cancer effect of the peptide vaccines. We also demonstrated the synergic effect of the peptide vaccination and intratumor injection of OK432 on anti-tumor effect and its mechanism through the efficient recruitment of systemically induced CTLs to the tumor sites.
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