Description du projet
La thérapie génique pour l’hépatite chronique
Le virus de l’hépatite B (VHB) peut entraîner une cirrhose et un carcinome hépatocellulaire, qui aboutissent à des millions de décès chaque année dans le monde. Étant donné que les mécanismes qui sous‑tendent la persistance du VHB sont mal compris, il n’existe aucun remède définitif et les traitements actuels visent à freiner le développement de la maladie hépatique. Le projet 2LIVEr, financé par l’UE, travaille sur une nouvelle stratégie pour réactiver la réponse inefficace des lymphocytes T CD8+ face au VHB, sur la base de la délivrance hépatocellulaire de l’interleukine‑2 (IL‑2) par des vecteurs lentiviraux. Cette approche de thérapie génique servira de traitement fonctionnel contre l’hépatite B chronique en activant le système immunitaire contre le virus.
Objectif
Hepatitis B virus (HBV) infections remain a major public health issue worldwide. Over 350 -400 million people are chronically infected by HBV, and about 1 million people die each year from the complications of this infection (cirrhosis and hepatocellular carcinoma) with a consequent hefty economic impact on national health systems. This led the World Health Organization to recognise HBV infection as a key priority and adopt the global health sector strategy to eliminate viral hepatitis, with a target of reducing new infections by 90% and mortality by 65% by 2030.
The risk of developing a chronic infection in healthy adults is due to a weaker, dysfunctional and narrowly focused CD8+ T cell response. Since the mechanisms underlying HBV persistence are not fully elucidated, current treatments (antiviral drugs and Interferon) aim to reduce the development of liver disease, while a definitive treatment for curing this infection is not yet available on the market.
Within the ERC Consolidator Grant 725038 “FATE”, we recently characterized the mechanisms behind the ineffective CD8+ T cell response towards HBV, demonstrating the potential efficacy of interleukin-2 (IL-2) – a cytokine – to reactivate it, thus achieving antiviral activity. This discovery, jointly with our proprietary third-generation, self-inactivating lentiviral vectors (LVs) that allow selective hepatocellular expression of IL-2, pave the way to single-dose gene therapy-based approach, a potential functional cure against chronic hepatitis B.
2LIVEr project intends to optimize and further validate our novel therapeutic approach from both a technical and commercial standpoint, moving from TRL3 to TRL4, thus fastening the roadmap towards the market.
Champ scientifique
Programme(s)
Régime de financement
ERC-POC-LS - ERC Proof of Concept Lump Sum PilotInstitution d’accueil
20132 Milano
Italie