Abstract 1041: Active interception to modulate the systemic cancer-permissive microenvironment and reduce cancer incidence in companion dogs with elevated cancer risk

Abstract Companion dogs have a lifetime cancer risk similar to that of humans. This excess risk, as compared to what is seen in other species, seems to be due to our recent success in outliving our evolutionarily adapted lifespan. For cancers to develop, a cancer-permissive environment must be present, which may exist months or even years before a tumor becomes detectable. We have developed the Shine On Suspicion (SOS) test, a flow cytometry based test to detect these changes that lead to a cancer-permissive environment. To make this test actionable, we combined it with a novel agent for cancer interception (secondary prevention) called eBAT. eBAT is a bispecific ligand targeted toxin consisting of truncated, deimmunized Pseudomonas exotoxin fused to epidermal growth factor (EGF) and the amino terminal fragment of urokinase. This drug was designed to use epidermal growth factor receptors (EGFR) and urokinase-type plasminogen receptors (uPAR) as baits to deliver the lethal toxin into the cells, rather than disrupting receptor signaling. eBAT has self-limiting, well-tolerated side effects and is safe enough for administration to otherwise healthy individuals. To date, eBAT has been administered to 11 healthy dogs that were determined to have elevated cancer risk based on the SOS test, with only 1 of the 11 dogs developing cancer more than 2 years after treatment. A hazard ratio calculated with a 95% confidence interval shows that dogs receiving eBAT interception had nearly 4 times reduction in risk of a cancer diagnosis compared to controls. Ongoing research aims to explore the identity and function of niche-forming cells to improve cancer prevention strategies and their applicability to humans. Citation Format: Ashley J. Schulte, Rose Dicovitsky, Taylor A. DePauw, Amber L. Winter, Kathleen L. Stuebner, Andrea Chehadeh, Sara Pracht, Antonella Borgatti, Ali Khammanivong, Mitzi Lewellen, Lauren E. Burt, Daniel A. Vallera, Michael S. Henson, Erin B. Dickerson, Christopher Ober, Kari L. Anderson, Esther Nell, Aaron L. Sarver, Gary R. Cutter, Jaime F. Modiano. Active interception to modulate the systemic cancer-permissive microenvironment and reduce cancer incidence in companion dogs with elevated cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1041.