IMMU-07. Messenger RNA challenge predicts cancer immunogenicity and response to checkpoint inhibitors

Background Cancer immunogenicity is predicated on activation of an immune response in the tumor microenvironment (TME) that can be perpetuated through use of immune checkpoint inhibitors (ICIs). HYPOTHESIS: Predicting which patients will respond to ICIs remains challenging with eligibility confined to tumor subtypes with microsatellite instability (MSI) and high mutational burden (TMB). These criteria are insufficient to identify ICI responsive patients. Methods To prospectively determine whether individual tumors will respond to immune checkpoint inhibitors (ICIs), we developed a novel mRNA tool to predict response ex vivo. By layering mRNA into multilamellar nanoparticles (ML RNA-NPs), multiple pathogen recognition receptors can be simultaneously activated in individualized cancer cells serving as a broad screen to test tumor immunogenicity. Results In our in vivo preliminary studies, we have observed brain tumor murine models that respond (i.e., GL261 and SMA-560 models) or do not respond (i.e., KR158b and CT2A models) to ICIs have been described. We then compared the cytokine profile secreted by in vitro treating these brain tumor cell lines with ML RNA-NPs using a novel 3D modeling system. Following ML RNA-NP challenge, 3D tumoroids elicited a similar pattern of cytokine response with increased IFN-β/IL6/CCL4 in GL261 and SMA-560, but not in KR158b-luc or CT-2A. Discussion/Conclusions Our results indicate that cytokine signatures following ML RNA-NP challenge differ significantly from ICI responsive versus non-responsive tumors. These findings allow for creation of a diagnostic assay to quickly assess tumor immunogenicity, allowing for informed immunotherapeutic treatment.