p53 Vaccine for Ovarian Cancer

P53 is the most commonly mutated gene in human cancers; it has been found to be mutated in almost 50% of ovarian cancers. Genetic mutation of p53 results in stabilization and increase in the level of the protein. In some cases, overexpression of p53 protein could also occur in tumors without detectable mutation in the open reading frame. Therefore, p53 could function as an antigen through two different mechanisms, as a mutant "foreign" protein and as a selfoverexpressed protein. The p53:264 - 272 wild type peptide has been shown to have high affinity for HLA-A2. It has also been shown to be naturally processed and endogenously

presented by HLA-A2 in different types of tumor cell lines for CTL recognition. These CTL

were able to lyse tumor cells overexpressing wild type or mutant p53 protein and failed to lyse

normal cells expressing normal levels of wild type p53.

In this protocol we will be vaccinating HLA-A2+ ovarian cancer patients who carry tumors which overexpress p53 with the wild type p53 peptide (264-272). This will be given either subcutaneously admixed with ISA-51 and GM-CSF adjuvants, or intravenously pulsed on dendritic cells along with low dose subcutaneous IL-2. In addition, those patients who express mutant p53 may also be vaccinated with a mutant p53 peptide, which corresponds to the mutation they harbor in their tumor, should the patients progress on the p53 (264-272) peptide.