PHASE I THERAPEUTIC AWARD: CHIMERIC NANOPARTICLE DELIVERY OF AN SARNA-BASED CANCER VACCINE FOR FAMILIAL ADENOMATOUS POLYPOSIS

Familial Adenomatous Polyposis (FAP) is a rare, inherited disorder typically caused by mutation of the adenomatous polyposis coli (APC) gene, a tumor suppressor gene involved in the Wnt signaling pathway that prevents uncontrolled cell growth. FAP is characterized by the development of hundreds to thousands of adenomatous (benign) polyps in the colon and/or rectum, and over the patient's lifetime there is an almost 100% likelihood that the disorder will develop into colorectal cancer. The field of cancer vaccines is continuously developing and has shown promise as a means of preventing development of cancers through immune stimulation against tumor-associated protein/peptides (neoantigens). Chimeron Bio's ChaESAR™ nanoparticle is a biosynthetic, self-assembling nanoparticle vector encasing a self-amplifying RNA (saRNA) capable of expressing one or more proteins of interest (POIs). In this study, we propose to develop a ChaESAR™ nanoparticle expressing mutated APC peptides as a cancer vaccine. Additionally, we will utilize the ChaESAR™ particle's multiplexing capabilities to co-express one or more additional neoantigens commonly observed in FAP, including (but not limited to) KRAS, ASXL1, Fbxw7, and Sox9, as a means of producing a more robust immune response against the disorder.