TARGETING INOS FOR IMPROVED THERAPEUTIC EFFICACY OF HPV CANCER VACCINES

Abstract

Human papillomavirus is the causative agent of cervical cancer, the most common cancer in women across the world. Therapeutic vaccines utilizing protein fragments (peptides) of HPV-16 E6 and E7 are being developed to induce protective immunity. The HPV peptide vaccine formulation currently being developed in the Sastry lab includes the adjuvant alpha-galactosylceramide (α-GalCer), which through activation of the innate immune natural killer T (NKT) cells enhances vaccine-specific immune responses. Non-proliferation and unresponsiveness in NKT cells has historically followed primary systemic administration of α-GalCer, but can be prevented using mucosal intranasal route of delivery. One reported result of α-GalCer administration is upregulation of the enzyme Inducible Nitric Oxide Synthase (iNOS), and upregulation of immunosuppressive cells as a consequence. I intend to determine the effect of α-GalCer on immunosuppression in our HPV-16 TC-1 cell line in contrast to literature reports. I will then determine the effect of iNOS inhibition on HPV peptide vaccination, using genetic and biochemical means. The beneficiary effects of iNOS targeting will then be evaluated in the context of multiple vaccinations and immunotherapy regimens.