CTL Based Therapeutic Vaccine to Prevent or Interrupt HPV Mediated Oncogenesis

Abstract Human PapillomavirusHPVis a cause inof the estimatedmillion new cases of cancer annuallyHPV associated cancers most commonly include female cervicaloropharyngealand anal cancerswith aboutnew cases anddeaths in the U Salone annuallyWhile preventive vaccination is availablecurrent vaccines are antibody based and do not slow or prevent the development of cancer from established HPV infectionand the burden of cancer from HPV is not expected to decline for decades worldwideThe need for noninvasive treatments is urgentCellular immunityparticular Thphenotype CDT lymphocytesCTLsare critical for clearing viral infections by recognizing and killing infected cellsCTLs are linked to the Major Histocompatibility Class IMHC Ipathway of processed antigens from cell cytoplasmUsually this compartment is accessed by live virusesand not by killed viruseslike the existing HPV vaccinesor proteinsFor this projectwe will harness a novel vectorthe endogenous humanvaultprotein nanoparticleas a therapeutic vaccine to interrupt and or treat HPV infection and HPV associated pre cancerWe have generated several prototype vaults containing different HPV antigens and our preliminary data demonstrates that our prototype HPV vault vaccines induce striking frequencies of both CDand CDT cells targeting the delivered antigensVault HPV vaccines activated betweenof total CDT cells andof total CDT cellsPreliminary studies on genital tractGTT lymphocytes post vaccination also indicated robust activation of CDand CDT cellsThis proposal will establish a candidate a CTLgenerating effective HPV vaccine Project Narrative Human PapillomavirusHPVis a remarkable contributor to cancerestimated to be a cause inof all cancersThe existing preventive vaccines do not generate the type of cellular immunity associated with clearance of virus infected cells and cancersand have no impact on established HPV infection that is destined to become malignantThis project aims to develop a novel vaccine vector that generates potent cellular immune responses for application as a therapeutic vaccine for the prevention and or treatment of HPV infections and HPV driven cancer