Project 2: Nucleic Acid Vaccines for the Chemoprevention of Ovarian Cancer Ovarian cancer is highly lethal. Despite the fact that the majority of patients will be diagnosed with advanced stage disease, 60% of those patients will obtain a complete remission with a combination of chemotherapy and surgery. Unfortunately, these remissions will not be sustained and over 70% of patients will relapse and eventually die from progressive ovarian cancer. New treatments and prevention strategies are needed for ovarian cancer. Vaccine directed against ovarian cancer antigens provide therapeutic potential. Recent studies, by several groups including our own, have shown patients with ovarian cancer have an immune response to their tumors and some antigens that are immunogenic in ovarian cancer have been defined. HER-2/neu (HER2) and mutant epidermal growth factor receptor (EGFRvIII) are over-expressed growth factor receptors present in 30 and 75% of ovarian cancers respectively. Both these proteins elicit immune responses in patients whose tumors express the proteins. Furthermore, preliminary studies in animal and/or human models suggest that antibodies directed against HER2 and EGFRvIII may mediate an anti- tumor response. Some patients against the tumor antigen. If these antibody responses could be boosted, via immunization, to potentially therapeutic molecular immunology and the definition of antigen recognition by T cells has allowed the identification of co-stimulatory molecules and soluble factors such as cytokines' which influence the immune environment. Nucleic acid vaccines (DNA vaccines) which are engineered to encoded both the appropriate co-stimulation and tumor antigen for the generation of growth factor specific antibody responses may allow significant levels of endogenous tumor specific antibodies to be generated.
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