Metabolically Enhanced Lactic Acid Bacteria for Boosting Cancer Therapy

Inter-individual variation in cancer therapy responses is significant, with a substantial fraction of patients not responding to treatment. This exposes non-responders to harmful side effects without benefit and results in vast resources being spent on eventually ineffective treatments. A key factor behind this variability is differences in microbiome composition and metabolism. However, translating microbiome-cancer research into live bacterial therapies that modulate the microbiome is challenging due to its complexity and heterogeneity. This project addresses this challenge using safe, robust, metabolically enhanced lactic acid bacteria capable of delivering therapy-boosting metabolites in the gut. We focus on metabolites naturally produced by gut bacteria that have been shown to enhance the efficacy of chemotherapy. The engineered bacteria will function as live biotherapeutics, ensuring the targeted delivery of metabolites directly in the gut and thus achieving physiologically beneficial pharmacokinetics. Our approach is distinct from other microbiome therapies due to its clear mechanism of action and the use of a unique platform developed in the ERC project ModEM. It enables rapid metabolic enhancement without genetic engineering, thereby reducing regulatory hurdles and accelerating market entry. Overall, the MELAB project aims to translate core findings from the ModEM project into a novel therapeutic adjuvant with the potential to benefit cancer patients by increasing therapy response rates.