Withdrawn Post Acceptance Asia-Pacific Vaccine and Immunotherapy Congress 2024

Recombinant Listeria Monocytogenes Vaccine Anti-tumor Response is Independent of the Host Inflammatory Cell Death Machinery (#153)

Abolaji S Olagunju 1 2 , Andrew V Sardinha 1 , Aamir Rana 3 , Gustavo P Amarante-Mendes 1 2
  1. Institute of Biomedical Sciences, Sao Paulo, CIDADE UNVERSITARIA, Brazil
  2. Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia (INCT), São Paulo, SP, Brazil
  3. Department of Immuno-Oncology, Beckman Research Institute, City of Hope, California, USA

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. Leveraging LM's capacity to provoke potent and targeted immune reactions against cancer, alongside the activation of in vivo antigen-specific CD8+ T cells, holds considerable promise. Notably, LM has been observed to activate inflammatory and immunogenic forms of cell death, including necroptosis and pyroptosis, thereby modulating immunological responses in a favorable manner. Importantly, the impact of host deficiencies in inflammatory cell death pathways on the effectiveness of LM-mediated anti-tumor immune responses remains unclear. In this study, we hypothesized that deficiencies in regulatory or effector molecules associated with pyroptosis or necroptosis would hinder the host's response to LM and consequently attenuate the stimulation of CD8+ T cell-mediated immunity. To test this hypothesis, we vaccinated intravenously wild-type (WT) C57Bl/6 mice alongside those lacking caspase-1/11, GSDMD, RIPK3, or MLKL with recombinant L. monocytogenes carrying the ovalbumin gene (LM.OVA). Subsequently, we conducted an in vivo cytotoxicity assay to assess the efficacy of OVA-specific CD8+ T lymphocytes in eliminating target cells. Additionally, we monitored the in vivo growth of B16 and B16.OVA melanoma cell lines in both control and vaccinated mice. Our findings indicate that although Caspase-1/11 and GSDMD participate at the control of LM-OVA infection, the deficiency of each of these molecules as well as RIPK3 or MLKL did not impair the antigen-specific anti-tumor response elicited by LM-OVA.