DDEL-13. ULTRASOUND-ENHANCED DELIVERY OF LIPOSOMAL DOXORUBICIN ACROSS THE BLOOD BRAIN BARRIER INDUCES AN IFN-GPHENOTYPE IN MICROGLIA, MACROPHAGES, AND T CELLS AND IMPROVES RESPONSE TO PD-1 BLOCKADE IN GLIOMAS

Abstract INTRODUCTION Given the limited drug penetration across blood-brain barrier (BBB), therapeutic potential of new and existing therapies has not been fully exploited for benefit glioblastoma (GBM) patients. METHODS Here we employed a novel delivery technology based on low-intensity pulsed ultrasound combined with intravenous microbubbles (LIPU/MB) that temporarily opens BBB to deliver liposomal doxorubicin (DOX) anti-PD-1 therapy (aPD-1) in mouse glioma models 3 recurrent GBM Immunological variables were evaluated tumor immune cells as well efficacy glioma-bearing mice treated DOX delivered by LIPU. These included measurement HLA ABC DR protein expression cells, microglia, macrophages IFN-g production glioma-associated microglia human tumors. We also assessed LIPU/MB enhanced combination mice. RESULTS Upregulation was observed cell lines at low concentrations DOX. Tumor from patients DOX, aPD-1 showed increased compared paired pretreatment samples. In both humans, absolute brain elicited specific phenotype MHC I humans. Furthermore, LIPU/MB-mediated opening peritumoral regions Combined treatment resulted long-term survival relied activity CD8+ T its efficacy. CONCLUSIONS Overall, this translational study demonstrates utility stimulate intracranial responses context gliomas.