IMMU-41. VERSATILE MRNA-NANOPARTICLE PLATFORM TO REPROGRAM THE BRAIN TUMOR MICROENVIRONMENT AND PREDICT TREATMENT OUTCOME

Abstract RNA vaccines have shown great promise as activators of immune responses against viral pathogens but their efficacy in cancer is unclear. Here, we describe a versatile, personalized mRNA-nanoparticle (RNA-NP) platform that can be customized to produce powerful anti-tumor activation, reprogram the brain tumor microenvironment, and predict vaccine just two days after treatment. Lipid mixtures (i.e. DOTAP, Cholesterol) with or without iron oxide nanoparticle-cores were complexed mRNA encoding antigens. Intravenous administration RNA-NPs induced robust activation innate cells resulting prolonged survival murine models subcutaneous intracranial melanoma. Inclusion cholesterol lipid backbone enabled delivery nucleic acids across blood barrier into tumor-associated myeloid GL261 KR158b tumors. These cholesterol-bearing liposomes not only activated microenvironment increased expression CD80 MHCII), also further manipulation this compartment. Use deliver siRNA targeting PD-L1 resulted significant reduction among associated cells, leading 37% long term survivorship combination systemic checkpoint blockade an otherwise fatal model GL261. We IONPs incorporated cores these particles enable non-invasive tracking dendritic by MRI, enabling creation theranostic approach to: 1) enhance immunologic effects; 2) facilitate translocation blood-brain barrier; 3) imaging response RNA-NPs.