Recombinant listeria monocytogenes vaccine induces antigen-specific anti-tumor immune response in inflammatory cell-death-deficient mice 2760

Abstract Description Recombinant Listeria monocytogenes (LM) emerges as a promising candidate for cancer vaccination, owing to its unique ability to replicate within the cytoplasm of host cells and its inherent accessibility to genetic manipulation, facilitating the expression of desired proteins. Vaccination strategies employing live LM have demonstrated significant efficacy in eliciting robust CD8 T cell responses, and fostering substantial immune priming; and activates inflammatory and immunogenic forms of cell death, such as necroptosis and pyroptosis. This study posits that defects in regulatory or effector molecules linked to pyroptosis or necroptosis might impair the host’s response to LM, hence diminishing the activation of CD8+ T cell-mediated immunity. To evaluate this concept, we administered recombinant L. monocytogenes containing the ovalbumin gene (LM.OVA) intravenously to wild-type (WT) C57Bl/6 and single deficient mice in caspase-1/11, GSDMD, RIPK3, or MLKL. We subsequently performed an in vivo cytotoxicity experiment to evaluate the effectiveness of OVA-specific CD8+ T lymphocytes in removing target cells. Furthermore, we observed the in vivo proliferation of B16 and B16.OVA melanoma cell lines in vaccinated or not mice. Our results show that Caspase-1/11 and GSDMD are involved in regulating LM-OVA infection, and the absence of either molecule, along with RIPK3 or MLKL, did not impede the antigen-specific anti-tumor response induced by LM-OVA. Funding Sources This study was supported by Ph.D. (Proc. No. 2021/12143-7) and M.Sc. (Proc. No. 2021/07624-6) fellowships from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP–Brazil). This work was supported by grants from FAPESP (Proc. No. 2018/25395-1; 2021/13486-5; 2023/02577-5) and CNPq (Proc. No. 308927/2019-2; 311122/2023-0; INCTiii 46543412014-2). Topic Categories Vaccines and Immunotherapy (VAC)