2002 Fiscal Year Final Research Report Summary
Experimental study on the vaccine therapy targeting p53 as a tumor antigen
| Project/Area Number |
12671251
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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 |
Digestive surgery
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| Research Institution | Wakayama medical school |
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Principal Investigator |
TANI Masaji Wakayama Medical School, Second Department of Surgery, assistant, 医学部, 助手 (60236677)
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| Co-Investigator(Kenkyū-buntansha) |
TANIMURA Hiroshi Wakayama Medical School, Second Department of Surgery, professor, 医学部, 教授 (10026990)
IWAHASHI Makoto Wakayama Medical School, Second Department of Surgery, assistant, 医学部, 講師 (70244738)
YAMAUE Horoki Wakayama Medical School, Second Department of Surgery, professor, 医学部, 教授 (20191190)
TSUNODA Takuya Wakayama Medical School, Second Department of Surgery, assistant, 医学部, 助手 (30275359)
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| Project Period (FY) |
2000 – 2002
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| Keywords | P53 / HLA-A24 / CTL / Binding assay |
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| Research Abstract |
We tested p53 encoded HLA-A24 binding peptides for their capacity to elicit anti tumor cytotoxic T lymphocytes (CTL) in vitro. These peptides were predicted from murine p53-derived cytotoxic peptides which being presented to CTL by H-2K^d and H-2K^b molecules. Because the HLA-A24 peptide binding motifs are similar to the H-2K^d and H-2K^b one. For CTL induction, we used CD8^+ T lymphocytes from peripheral blood mononuclear cells (PBMC) of a healthy donor and peptide pulsed autologous dendritic cells (DC) as antigen presenting cells (APC). We can identify a peptide, PU161 (AIYKQSQHM), which was capable of eliciting CTL lines that lysed tumor cells expressing HLA-A24 and p53. The effectors lysed C1RA24 cells ( p53^+, HLA-A^*2402 transfectant), but not its parent cell lines C1R ( p53^+, HLA-A, B, C null cell). These results indicate that the cytotoxic activity of the CTL showed HLA-A24 restricted manner. In addition, to potentially increase binding affinity and immunogenicity while retaining p53 specificity, we investigated a new synthetic peptide (PU161Y2L9 : AYYKQSQHL) modified at anchor residues to enhance binding to HLA-A24.
The identification of this novel p53 epitope for CTL offers the possibility to design and develop epitope based immunotherapeutic approaches for treating HLA-A24 positive patients with tumors that express p53.
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