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Identifying novel cytolytic T lymphocyte epitopes of follicle-stimulating hormone receptor for the design of DNA launched nanoparticle vaccines against ovarian cancers
Ovarian cancers represent a significant public health issue, with over 20,000 new diagnoses each year in the United States. Patient prognoses are closely tied to the time of detection; patients that are diagnosed early and begin interventions exhibit 5-year survival rates of over 90%, while at later stage diagnoses survival rates fall to only ~30%. Unfortunately, over 75% of patients with ovarian cancer are diagnosed at advanced stages. Therefore, there is a critical unmet need for innovative new strategies for earlier detection and prevention of ovarian cancers.
Our group has previously shown that DNA-launched nanoparticle vaccines (DLNPs) induce stronger antibody responses and uniquely induce tumor-killing cellular responses compared to conventional vaccines. I have shown that DLNP vaccination can achieve complete tumor rejection in multiple models of cancer, including HPV-induced tumors; ~16% of ovarian cancers are associated with HPV. However, for a prophylactic vaccination strategy to be effective, it needs to achieve coverage against a large proportion of ovarian cancers. Here I propose to examine follicle-stimulating hormone receptor (FSHR), a receptor expressed in 50-60% of ovarian cancers, to identify its portions that induce the greatest tumor-killing immune responses. I will then design and characterize DLNPs displaying these portions. In combination therapy with my HPV DLNPs, I will evaluate these novel FSHR DLNPs in multiple ovarian cancer models compared to conventional vaccine formulations and explore the immune mechanisms underlying their efficacy in preventing ovarian cancers.