Vaccine Therapy With Tumor Specific p53 Peptides in Adult Patients With Low Burden Adenocarcinoma of the Ovary
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
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)
Masking: Open Label, Primary Purpose: Treatment
Cellular immunity as measured by Elispot assay and 51 Cr-release assay at baseline and every 3 weeks.
Steven A Rosenberg, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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