IMMU-06. SYSTEMIC MRNA VACCINES RESET IMMUNOGENICITY AGAINST DIFFUSE MIDLINE GLIOMA

Abstract BACKGROUND DIPG remains a uniformly fatal disease in dire need of new therapies. There are currently no systemic therapies with proven efficacy against these tumors. To overcome barriers, we developed mRNA lipid particle (LP) vaccine that localizes to tumors and reticuloendothelial (RE) organs modulate both innate adaptive immunity poorly immunogenic like DIPG. OBJECTIVE We sought assess whether RNA-LPs encoding for model antigens (e.g. H3K27M) would reprogram simultaneously elicit sustained diffuse midline glioma (DMG). RESULTS RNA-LP massive recruitment nearly all monocytes lymphocytes RE secondary danger response mediated by release orchestrated cytokines (IL-12, TNF-α, IFN-α) chemokines (CCL2, CCL4, CXCL9-10). This corresponds increases absolute numbers activated DCs T cells the mice reprogramming tumor microenvironment canines (pet dogs spontaneous disease). In neonatal inoculated established murine K2 gliomas, observed vaccines H3K27M (beginning at ~day 30) significant long-term survivorship, which appears curative bulk animals treated. While specific constructs appeared superior, improved survivorship irrelevant species (i.e. pp65 GFP) suggesting be particularly sensitive immune modulation. DMGs, clinical symptomatology edema/hydrocephalus followed improvement many pseudoprogression from intratumoral inflammation remodeling. CONCLUSION effect making them ‘hot.’ Treatment responses models advanced DMGs encouraging. advancing final formulation FDA-IND submission early phase trials through multi-institutional consortia.