Experimental study on the vaccine therapy targeting p53 as a tumor antigen

点击翻译按钮获取中文摘要

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.