Abstract ▼ AI-Helper

AbstractA growing appreciation of the relationship between the immune system and tumorigenesis has led to the development of strategies aimed at ‘re-editing' the immune system to kill tumors. Here, we report a novel tactic for overcoming the activation-energy threshold of the immunosuppressive...

AbstractA growing appreciation of the relationship between the immune system and tumorigenesis has led to the development of strategies aimed at ‘re-editing' the immune system to kill tumors. Here, we report a novel tactic for overcoming the activation-energy threshold of the immunosuppressive tumor microenvironment and mediating the delivery and presentation of tumor neoantigens to the host's immune system. This nature-derived nanocage not only efficiently presents ligands that enhance cancer cell phagocytosis, it also delivers drugs that induce immunogenic cancer cell death. The designed nanocage-therapeutics induces the release of neoantigens and danger signals in dying tumor cells, and leads to enhancement of tumor cell phagocytosis and cross-priming of tumor specific T cells by neoantigen peptide-loaded antigen-presenting cells. We observed potent inhibition of tumor growth and complete eradication of tumor through systemic tumor-specific T-cell responses in tumor draining lymph node and spleen and further, infiltration of CD8+ T cells into the tumor site. Remarkably, after removal of the primary tumor, all mice treated with this nanocage-therapeutics are protected against subsequent challenge with the same tumor cells, suggesting development of lasting, tumor-specific responses. This designed nanocage-therapeutics ‘awakens' the host's immune system and provokes a durable systemic immune response against cancer.Citation Format: Gihoon Nam, Gi Beom Kim, In-San Kim. Nanocage-therapeutics prevailing phagocytosis and immunogenic cell death awakens immunity against cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5685.