OTHR-05. A LIVING EX VIVO PLATFORM FOR FUNCTIONAL, PERSONALIZED PEDIATRIC BRAIN CANCER DIAGNOSIS

Functional precision medicine platforms are emerging as promising strategies to improve pre-clinical drug testing and guide clinical decisions. We have developed an organotypic brain slice culture (OBSC)-based platform and multi-parametric algorithm which enable rapid engraftment, treatment, and analysis of fresh patient brain tumor tissue and patient-derived cell lines. The platform has supported engraftment of every patient tumor tested to this point: high- and low-grade adult and pediatric tumor tissue rapidly establish on OBSCs among endogenous astrocytes and microglia while maintaining the tumor’s original DNA profile. Our algorithm calculates dose-response relationships of both tumor kill and healthy tissue toxicity, generating summarized drug sensitivity scores based on therapeutic window and allowing us to normalize response profiles for a panel of FDA-approved and exploratory agents. Summarized patient tumor scores after OBSC treatment revealed positive associations to clinical outcomes, suggesting the OBSC platform can provide rapid, accurate, functional testing to ultimately guide patient care.