Roswell Park Ovarian Cancer SPORE

OVERALL SUMMARY – Roswell Park-University of Chicago Ovarian Cancer SPORE This is the revised competing renewal application of the Roswell Park-University of Chicago Ovarian Cancer SPORE. We have made significant progress on the translational objectives and human endpoints of each Individual Research Project (IRP). Our highly successful Developmental Research Program (DRP) and Career Enhancement Program (CEP) have catalyzed new translational ovarian cancer research projects, collaborations, and extramural funding for awardees. Our overarching goal remains unchanged: to conduct multidisciplinary, mechanism-based and collaborative translational research that will have the highest possible impact for patients with ovarian cancer. Because immunotherapies have met with only modest success in ovarian cancer patients, we continue to uniquely focus on novel strategies for generating effective anti-tumor immunity by unraveling immune-resistance mechanisms and identifying novel proteogenomic biomarkers of responsiveness. After significant planning and guidance by our Internal and External Advisory Boards, and Patient Advocate Committee, we have leveraged our highly successful DRP and CEP to propose two bi-directional translational IRPs addressing basic and clinical research questions of importance in ovarian cancer. The new IRP1 evolved as a result of a DRP award and the new IRP2 developed from a CEP award. IRP1 will test an oncolytic virus armed with a CXCR4 antagonist in combination with PDL1 blockade to abrogate tumor immune suppression and limit T cell exhaustion in a randomized Phase I/II clinical trial. IRP2 addresses the completely novel concept of identifying mismatch between immunopeptidomes of ovarian cancer cells versus dendritic cells and leveraging a computational approach of bypassing such mismatch. IRP1 commences with a planned clinical trial; the Phase I/II clinical trial in IRP2 will commence in year 3 following preclinical, IND-enabling translational studies. The program also continues to expand opportunities for new avenues of ovarian cancer translational research via its successful DRP and CEP. The four highly integrated, interconnected shared resource cores – Administration, Biospecimen & Pathology, Biostatistics & Bioinformatics, and Immunogenomics – bring innovative technology and resources to the SPORE and do not duplicate pre-existing shared resources available at Roswell Park or the University of Chicago. This application is strongly supported by over $3.6MM of institutional commitment to ensure its success of conducting highly innovative translational research that changes the clinical practice paradigm in ovarian cancer.