Abstract 2209: MaaT034, a new co-cultured microbiome ecosystem therapy candidate, is capable to safely colonize the gastro-intestinal tract of germ-free mice to restore a healthy gut physiology and to stimulate immunity

Abstract Background: Increasing evidence suggests that gut microbiome composition modulates tumor response to therapies, including immune checkpoint inhibitors (ICI). Clinical proofs of concept were obtained in pilot studies using healthy or ICI-responder donor-derived fecal matter transplants to modulate the gut microbiome of non-responding cancer patients and improve their response to ICI. We have developed Microbiome Ecosystem TherapiesTM (MET) replicating at large industrial scale the effects of ICI-responders gut microbiome. MaaT034, the first-in-class co-cultured microbiome product, has been selected through artificial intelligence and in vitro screening assays to optimize intestinal homeostasis and to activate immune functions alone and in combination with an ICI treatment. Method: We used germ-free mice to evaluate MaaT034 engraftment and safety, as well as its impact on metabolite production, immunity as well as gut morphology. Results: Metagenomic analysis demonstrates that MaaT034 is capable of engrafting in the gut of germ-free mice, as evidenced by the presence of the four major phyla of the human product in mice. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed the presence of genes involved in the synthesis of key metabolites such as short chain fatty acids, indoles, as well as secondary biliary acids. In line, metabolite quantification in the feces of mice further confirmed the capability of MaaT034 microbes to produce these metabolites. MaaT034 was able to improve the gastrointestinal physiology and to stimulate immunity in germ-free mice (reduction of the size of cecum, increase in the depth of intestinal crypts, increase in the percentage of Goblet cells, increase of spleen weight). All mice remained healthy throughout the experiment and no adverse event was observed. Conclusion: Altogether, these findings underscore MaaT034's potential to safely colonize the gastro-intestinal tract of mice and to produce key metabolites allowing to restore a healthy gut physiology and to stimulate both local and systemic immunity. As such, MaaT034 could offer a promising therapeutic benefit for the treatment of solid tumors in combination with ICI therapy. Citation Format: Bastien Laperrousaz, Julie Reygner, Charlotte Petitjean, Aurore Duquenoy, Cyrielle Gasc, Diane Plouchart, Sophie Declomesnil, Carole Schwintner, Nathalie Corvaïa. MaaT034, a new co-cultured microbiome ecosystem therapy candidate, is capable to safely colonize the gastro-intestinal tract of germ-free mice to restore a healthy gut physiology and to stimulate immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2209.