Project Grant R44CA275489

DEVELOPMENT OF A THERAPEUTIC SAPNANO-ESO VACCINE FOR PROSTATE CANCER - PROJECT SUMMARY/ABSTRACT PROSTATE CANCER IS A LEADING CAUSE OF CANCER-RELATED DEATHS OF MEN IN THE UNITED STATES AND WORLDWIDE. IMMUNOTHERAPY IS A PROMISING APPROACH, BUT HAS NOT PROVEN SUCCESSFUL YET IN PROSTATE CANCER. HENCE, METASTATIC PROSTATE CANCER REMAINS AN IMPORTANT UNMET MEDICAL NEED. TO ADDRESS THIS UNMET MEDICAL NEED, WE RECENTLY DEVELOPED A NOVEL VACCINE TECHNOLOGY, CALLED SELF-ASSEMBLED PEPTIDE NANOPARTICLES (SAPNANO) VACCINES. IMMUNOVA THERAPEUTICS IS A STARTUP COMPANY WITH THE MISSION TO FURTHER DEVELOP THE SAPNANO-ESO VACCINE PRODUCT (OR IMT-001) FOR THE TREATMENT OF NY-ESO-1 POSITIVE CANCER, INCLUDING PROSTATE CANCER. THIS IMT-001 PRODUCT INDUCES ROBUST ANTITUMOR RESPONSES, RESULTING IN MARKED INHIBITION OR EVEN ELIMINATION OF PROSTATE TUMOR CELLS IN A MOUSE MODEL. THE KEY FEATURES OF THE ITM-001 PRODUCT INCLUDE INTRAVENOUS DELIVERY WITHOUT DENDRITIC CELLS AND THE ABILITY TO INDUCE ROBUST AND THERAPEUTIC ANTITUMOR IMMUNITY, WHICH IS DISTINGUISHED FROM OTHER VACCINE TECHNOLOGIES THAT FAIL TO INDUCE THERAPEUTIC IMMUNITY. INCREASING EVIDENCE SUGGESTS THAT THE MAINTENANCE AND EXPANSION OF VACCINE-INDUCED T CELLS MAY BE INHIBITED BY MULTIPLE SUPPRESSIVE MECHANISMS AT TUMOR SITES, INCLUDING THE INTRINSIC CO-INHIBITORY PD-1/PD-L1 SIGNALING, TREG CELLS, TUMOR-ASSOCIATED MACROPHAGES AND MDSCS, THUS POSING MAJOR OBSTACLES FOR EFFECTIVE VACCINE AND IMMUNOTHERAPY. IT IS LIKELY THAT IMT-001 VACCINE- INDUCED ANTITUMOR IMMUNITY COULD BE FURTHER ENHANCED BY ANTI-PD-1 BLOCKADE. IN THIS APPLICATION, WE WILL DETERMINE THE STABILITY OF IMT-001 VACCINE PRODUCT IN VITRO AND OPTIMAL DOSES AND DELIVERY ROUTES FOR THERAPEUTIC ANTITUMOR IMMUNITY IN MOUSE TUMOR MODELS (AIM 1), CONDUCT INVESTIGATIONAL NEW DRUG (IND)-ENABLING STUDIES OF THE BIODISTRIBUTION AND PHARMACOLOGICAL TOXICITIES (AIM 2), AND FINALLY TEST WHETHER IMT-001 VACCINE-INDUCED THERAPEUTIC ANTITUMOR IMMUNITY CAN BE FURTHER ENHANCED BY OF PD-1 BLOCKADE THERAPY (AIM 3). UPON COMPLETION OF THE PROPOSED STUDIES, WE SHOULD HAVE COMPLETED THE IND-ENABLING STUDIES AND ARE WELL POSITIONED TO SUBMIT AN IND FOR A PHASE I CLINICAL TRIAL. THIS SBIR SUPPORT IS CRITICALLY IMPORTANT FOR IMMUNOVA THERAPEUTICS TO ACCELERATE THE DEVELOPMENT OF NEW CANCER VACCINE PRODUCT/DRUG FOR THE TREATMENT OF METASTATIC PROSTATE CANCER, AS WELL AS OTHER NY-ESO-1 POSITIVE CANCERS.