Abstract B052: Recombinant Listeria-Monocytogenes Vaccine Induces Anti-tumor Immune Response in Inflammatory Cell Death Machinery-Deficient Mice

Abstract Recombinant Listeria monocytogenes (LM)-based cancer vaccines show an optimistic immunotherapeutic approach for treating cancer. Employing LM's unique capacity to stimulate strong and targeted anticancer immune responses and activation of in vivo antigen-specific CD8+ T cells. LM has been shown to trigger inflammatory and/or immunogenic cell death processes, including necroptosis and pyroptosis, to modulate immunological responses positively. Nevertheless, the consequence of the deficiency of the host inflammatory cell death machinery on the efficacy of LM to induce an effective anti-tumor immune response remains unresolved. Therefore, we projected that a deficiency in regulatory or effector molecules involved in necroptosis or pyroptosis would interfere with the host response to LM and the consequent stimulation of CD8+ T cell-mediated immunity. To test our hypothesis, wild-type (WT), caspase-1/11-/-, gsdmd-/-, ripk3-/-, and mlkl-/-C57Bl/6 mice were vaccinated with recombinant L. monocytogenes carrying the ovalbumin gene (LM.OVA) intravenously. An in vivo cytotoxicity assay was carried out to assess the efficiency of target cell elimination by OVA-specific CD8+ T lymphocytes. In addition, the in vivo growth of B16F0 and B16F0.OVA melanoma cell lines were measured in control and vaccinated mice. Our findings showed that Caspase-1/11 and GSDMD help control LM-OVA infection, but a single deficiency of either of the molecules did not affect the LM-OVA-induced antigen-specific anti-tumor response. Citation Format: Abolaji S Olagunju, Andrew Diniz Victor Sardinha, Gustavo P. Amarante-Mendes. Recombinant Listeria-Monocytogenes Vaccine Induces Anti-tumor Immune Response in Inflammatory Cell Death Machinery-Deficient Mice [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2024 Oct 18-21; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2024;12(10 Suppl):Abstract nr B052.