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Reprogramming Listeria monocytogenes flavin metabolism to improve its therapeutic safety profile and broaden innate T-cell activation
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Reprogramming Listeria monocytogenes flavin metabolism to improve its therapeutic safety profile and broaden innate T-cell activation
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Journal Article
Reprogramming Listeria monocytogenes flavin metabolism to improve its therapeutic safety profile and broaden innate T-cell activation
2025
Overview
Listeria -based live-attenuated cancer vaccines represent a promising therapy in many different pre-clinical tumor models and in clinical trials. Enhancing its anti-cancer immunity and increasing its safety profile will advance the clinical applications of Listeria vaccines. By manipulating Listeria monocytogenes flavin metabolism, we engineered a quadruple attenuated intracellular Listeria (QUAIL) vaccine candidate strain that has limited toxicity associated with extracellular growth in major extracellular niches in vivo, including blood and implanted catheter ports. Furthermore, we showed that QUAIL can be effectively programmed to engage innate-like T cells known as mucosal-associated invariant T cells, which could be harnessed for future cancer immunotherapies. The results presented here lay the foundation for further analysis of QUAIL as a safer, yet immunopotent L. monocytogenes vaccine or therapeutic vector.
Publisher
American Society for Microbiology
Subject
/ Clinical Microbiology and Infectious Diseases
/ Intracellular Pathogen Survival
/ Intracellular Survival Mechanisms
/ Intracellular Survival of Listeria
/ Intracellular Survival Strategies
/ Mechanisms of Intracellular Survival
/ Microbial Pathogenesis and Immunology
/ Pathogen Biology and Host Interaction
/ Vaccines
