Abstract C005: Tumor vaccines and oncolytic virotherapy: systemic immunity vs. tumor microenvironment

Abstract

Abstract Tumor vaccines, particularly the innovative mRNA variants, hold immense promise in cancer immunotherapy. Despite their potential, these vaccines encounter formidable challenges in surmounting immune tolerance, the immune-suppressive tumor microenvironment (TME) and more importantly, the resistance developed in cancer cells that are antigen negative. Concurrently, oncolytic virotherapy (OV), a distinct facet of tumor vaccination, significantly alters the TME and releases tumor antigens via lysis to generate a broader spectrum of tumor antigens. This unique property positions OV to induce anti-tumor immunity, as evidenced by prolonged overall survival and abscopal tumor suppression. Recognizing the complementary strengths of mRNA tumor vaccines and OV, we propose a combined approach to address the limitations inherent in each modality. Our study tested this hypothesis by combining a mRNA vaccine targeting HER2 with oncolytic viruses, utilizing a prime-boost strategy on a HER2-expressing CT26 mouse tumor model. Notably, while the mRNA vaccine alone induced specific anti-HER2 systemic immunity, the combination demonstrated a potent immune response against both anti-HER2 and anti-CT26, leading to durable tumor eradication. Our findings highlight that peripheral vaccination has the potential to elicit an immune response in non-immune suppressive environments. However, combining it with virotherapy not only amplifies specific immunity but also induces a broader immune response against a spectrum of tumor antigens. This synergistic combination represents a promising avenue for advancing cancer immunotherapy, offering the potential for improved treatment outcomes and broader applicability of tumor vaccines across diverse cancer types. Citation Format: William Jia. Tumor vaccines and oncolytic virotherapy: systemic immunity vs. tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C005.