Development of a vault nanovaccine for pancreatic cancer immunotherapy

Project Summary Abstract The goal of this application is to apply our vault nanocapsule platform for the development of a survivinvault therapeutic vaccine to treat pancreatic cancerFor the pastyearsthere have been no notable improvements to patient survivalInit is estimated thatpeople will be diagnosed with pancreatic cancer andwill die from the diseasein the US aloneTreatment with a therapeutic cancer vaccine stimulates the patient s immune system to develop a specific anti tumor response and is a promising strategy for cancer immunotherapySafe and effective delivery of the vaccine is necessary for successful treatmentDelivery vehiclesincluding liposomesvirus like particles and bacterial vectorshave been employedhoweverimmunogenicity of these vehicles prevent booster dosing which is necessary to achieve a sustained anti tumor responseCell based therapies overcome the inadequacy of most delivery vehiclesbut manufacturing is expensivetime consuming and inefficientVault nanocapsules are uniquenatural hollow protein shells that are biodegradablebiocompatiblenon toxic and non immunogenicFound in the cytoplasm of most eukaryotic cellsvaults may naturally function to bring antigens for presentationSurvivin is a tumor associated antigen broadly expressed by tumorsincluding pancreatic ductal adenocarcinomaThe vault nanocapsule is the only true natural human nanoparticle and the only nanocapsule that has the potential to deliver antigens through a natural pathwayOur proprietary and patent pending technologies for the vault nanocapsule platform will make the survivin vault nanovaccine a safe and effective cancer treatment for pancreatic cancerIn this proposalwe willproduce vault nanocapsules that encapsulate survivinassess the magnitude and potency of the immune response following immunization with the survivin vault nanovaccineandcharacterize the therapeutic anti tumor immune response stimulated by the survivin vault vaccine in an orthotopic KrasGDTrpRHPDXCreKPCmurine model of pancreatic cancerIn the Phase II STTRthe efficacy of our survivin vault nanovaccine will be further validated using an autochthonous KPC tumor model for advanced metastatic pancreatic cancer and the production will be converted to comply with current good manufacturing practicecGMPregulationsthus enabling preparation of an IND application for clinical testing Project Narrative Pancreatic cancer is a deadly disease that has a dismalyear survival rate ofTo overcome the immunosuppressive tumor microenvironment and poor tumor antigenicitywe propose using the vault nanocapsule for the delivery of a therapeutic cancer vaccine that targets survivina tumor associated antigen predominantly expressed in cancer cellsOur vault nanocapsule platform has the potential to stimulate an effective survivin specific T cell response that will promote a sustained protective anti tumor immunity and lead to prolonged patient survival