Descrizione del progetto
Vescicole batteriche extracellulari contro il cancro
Come le cellule eucariote, i batteri secernono vescicole extracellulari di dimensione nanometrica dotate di un carico attivo, quali le proteine, come meccanismo di comunicazione con altri batteri e con l’ospite. Gli scienziati coinvolti nel progetto MICROBE, finanziato dall’UE, avevano precedentemente scoperto che il microbiota intestinale secerne anche vescicole batteriche extracellulari nella circolazione sistemica di pazienti con una maggiore permeabilità intestinale. Il significato biologico di queste vescicole nell’interazione tra ospite e batteri è ancora per lo più sconosciuto. Attraverso la caratterizzazione approfondita delle vescicole batteriche extracellulari di soggetti sani e pazienti con una maggiore permeabilità intestinale, MICROBE intende esaminare come tali vescicole influiscano sul corso della malattia.
Obiettivo
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.
Campo scientifico
- 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
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-ERC - HORIZON ERC GrantsIstituzione ospitante
9000 Gent
Belgio