(447g) Delivery of RNA Editing Machinery Enhances Immunogenicity of Cold Tumors

Immune checkpoint inhibitors (ICIs) have revolutionized cancer immunotherapy but remain effective in only a subset of patients and tumor types. The successful treatment of tumors that lack T cell infiltration, known as immunologically cold tumors, remains a major roadblock in cancer immunotherapy. Tumors with high mutational burden consistently respond better to ICI due to the abundance of new proteins or “neoantigens” that become recognizable by the immune system. Here, we deliver RNA editing machinery to alter codons and ultimately protein expression to induce the formation of neoantigens in tumor cells and unmask them to the immune system. We test this approach in a highly aggressive, immunologically cold model of murine melanoma and show significant reduction in tumor growth and increase in overall survival compared to ICI alone. This approach has the potential to expand the use of ICIs in the clinic through combination therapy and enhance our understanding of the role of neoantigens in ICI treatment.