Human Papilloma Virus (HPV) types 16 and 18 are detected in roughly 70% of all invasive cervical tumors. Among cytologically normal women, detection of HPV infection by PCR has been shown to increase the subsequent risk of cervical cytologic abnormalities by 12 fold, suggesting that effective vaccines (preventive/therapeutic) for HPV infection would be a useful medical advance in the battle against this cancer. EpiVax is developing a dendritic cell-directed DNA vaccine against HPV 16, 18, and other cervical cancer-associated HPV types. For this project, we have selected 100 novel HPV peptides that represent putative MHC class I and class II restricted T cell epitopes, primarily derived from the E1, E2, E6, E7 and L1 proteins of selected HPV types. Binding studies and CTL studies will be performed to select the best candidates for vaccine development Selected epitopes will be inserted in a DNA vector. Additional DNA vaccine development, safety, toxicity, and protection studies will be carried out in Phase II.
The specific aims of this project are to: * Screen putative HPV epitopes for MHC binding and HPV-specific T cell recognition * Construct DNA vaccine vectors containing candidate HPV epitopes * Evaluate DNA vector expression in human dendritic cells in vitro.
A therapeutic anti-HPV vaccine would have a tremendous market impact since existing cervical screening programs cost nearly $6 billion annually in the United States. Also, most sexually active women have been exposed to HPV, so it is unlikely that a prophylactic HPV vaccine will confer protection. A novel immunologic therapy to treat existing HPV infection as well as HPV-associated cervical cancer, such as the one we propose, may represent an attractive and cost effective treatment alternative.
