Description du projet
Des vésicules extracellulaires bactériennes contre le cancer
Tout comme les cellules eucaryotes, les bactéries sécrètent des vésicules extracellulaires (VEB) de taille nanométrique chargées d’un matériel actif tel que des protéines, comme mécanisme de communication avec d’autres bactéries et avec l’hôte. Les scientifiques du projet MICROBE, financé par l’UE, avaient précédemment découvert que le microbiote intestinal sécrétait également des VEB dans la circulation systémique des patients présentant une plus grande perméabilité intestinale. L’importance biologique des VEB dans les interactions entre l’hôte et les bactéries est encore très peu connue. Grâce à une caractérisation approfondie des VEB provenant d’individus sains et de patients présentant une forte perméabilité intestinale, MICROBE entend étudier la manière dont les VEB influencent l’évolution de la maladie.
Objectif
Emerging evidence from cancer patients and mouse models indicates that gut bacteria affect response to immune checkpoint inhibitors (ICI). As a result, modification of gut bacteria by dietary changes, probiotics and fecal transplantations are explored but a huge gap remains to gain clinical application. Limiting factors are the lack of mechanistic knowledge on how gut bacteria impact ICI response, the need of antibiotics to treat infections in cancer patients and gut resilience to exogenous bacterial colonization. Bacteria release nanometer-sized extracellular vesicles (BEV), loaded with specific pathogen-associated molecular patterns (PAMP), which possess multiple favorable characteristics for clinical application but remain minimally explored in oncology. Recently, my research group pioneered the discovery of gut-derived immunomodulatory BEV in the systemic circulation (sysBEV) of non-septicemic cancer patients. I hypothesize that sysBEV direct ICI response by initiating cytokine release to instruct innate and adaptive anti-tumor immunity. The overall scientific objective of my ERC-CoG project is to establish an innovative nanotherapeutic strategy using non-replicating BEV nanoparticles as a game changer to establish a safe but potent and durable ICI response. Hereto, MICROBE will analyze cancer patient biospecimens to address a number of fundamental questions with regard to BEV characteristics that are essential to ICI response and implement this know-how to formulate BEV nanotherapeutics from gut bacteria of healthy donors and ICI responsive cancer patients. The optimal administration route, treatment dosage, pharmaco-kinetics and -dynamics will be established and the synergism between BEV nanotherapeutics and ICI will be elucidated using clinically relevant mouse models. In conclusion, MICROBE will provide the EU a frontrunner position for a future first-in-human clinical trial using BEV nanotherapeutics in anti-cancer treatment.
Champ scientifique
- natural sciencesbiological sciencesmicrobiologybacteriology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmacokinetics
- medical and health sciencesclinical medicinetransplantation
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
9000 Gent
Belgique