Translation of Evolved Oncolytic Virotherapy Product for Colorectal Cancer Treatment

About This Grant

Project Summary/Abstract Colorectal cancer is diagnosed in an estimated 1.93 million new patients and causes nearly 1 million deaths per year worldwide, numbers that are unfortunately predicted to rise. Immunotherapies, including CAR-T cells (which involve T-cell targeting of a tumor-associated antigen) and checkpoint inhibitors (which stimulate adaptive immune responses by blocking signals that inhibit immune cells), have substantially advanced oncology but suffer low response rates in solid tumors that suppress immune responses. Oncolytic virotherapies, viral vectors engineered to selectively replicate within and deliver genetic cargo to tumors, are an immunotherapeutic modality that can combine and elevate the advantages of both CAR-T and checkpoint inhibitor therapies by mediating multi-antigen targeting of immune cells to tumors and expression of multiple cargoes to overcome immunosuppressive tumor microenvironments. However, oncolytic virotherapies are challenged by limited delivery efficiency, including poor biodistribution to tumors and limited dissemination of therapeutic cargo within and among metastasized sites. To overcome these challenges, Vivere Oncotherapies, Inc. is advancing its evolved oncolytic virotherapy product, OV-151, to the clinic. OV-151 confers improved delivery, lowered tumor burden, and increased survival for in vivo murine models of colorectal cancer. Here, we propose three aims to advance OV-151 as a clinical therapeutic candidate: 1) characterize the delivery properties of our lead clinical vector to tumors in vitro and in vivo, 2) characterize and optimize cargo to deliver using our vector, and 3) develop an inducible promoter to synergize potent immunostimulatory cargo expression with improved tumor-specific delivery efficiency. Successful completion of these aims—which include precursor experiments toward optimizing manufacturing and purification processes—will yield a strong basis for future execution of IND-enabling studies, submission of a Phase II SBIR application, and preparation for an FDA INTERACT meeting. Throughout this process, the Small Business Transition Fellow applicant, Dr. Adam Schieferecke, PhD, will be supported in his work daily by his fellow full-time Vivere personnel member (Dr. Hyuncheol Lee, DVM, PhD), weekly by his highly accomplished business and technical mentors (Drs. Melissa Kotterman and David Schaffer, respectively) who have also committed to completing the NIH I-Corps program with him, bi-weekly with his scientific advisory board mentors (Drs. Phung Gip and David Raulet), and bi-quarterly with his investor and physician KOL (Drs. Tony Kulesa and Brad Stohr, MD, PhD, respectively).