| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
The p53 gene has been shown to be frequently mutated, therefore, the p53 protein is an attractive candidate for the development of broadly applicable vaccine therapies. In this study, we identified the wt p53_<110-124> peptide as a naturally presented epitope. We then demonstrated the ability of anti-wild-type p53_<110-124> CD4+ T cells to enhance the generation and antitumor functions of CD8+ effector cells. Next, we investigated anti-wild-type p53 CTL response of peripheral blood mononuclear cells(PBMC) obtained from healthy donors and cancer patients in IFN-γ ELISPOT assays. Interestingly, PBMC obtained from patients who had an altered p53 accumulation showed lower frequency of anti-wild-type p53 CTL in some of peptides tested, as compared with those who had no p53 accumulation. Thus, examination of the relationship between the pattern of p53 accumulation of tumor cells and the CTL response to wild-type p53 peptides may be important for the development of p53-based cancer vaccines. On the other hand, for elucidation of immunological abnormalities in cancer patients, the proportions and phenotype of dendritic cells(DCs) were investigated. The percentage of myeloid DCs was significantly lower and expression of HLA-DR was significantly decreased in total and myeloid DCs of cancer patients compared to healthy donors. Thus, an imbalance in subpopulations or maturation stages of circulating DCs could reflect the state of cancer-related immunosuppression.
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