Descrizione del progetto
Terapia genica per l’epatite cronica
Il virus dell’epatite B (HBV) può portare alla cirrosi e al carcinoma epatocellulare, facendo registrare fino a un milione di decessi all’anno nel mondo. Poiché i meccanismi di fondo della persistenza dell’HBV sono ancora poco chiari, non esiste una cura definitiva e gli attuali trattamenti sono volti essenzialmente a ridurre lo sviluppo dell’epatopatia. Il progetto 2LIVEr, finanziato dall’UE, sta lavorando a un’innovativa strategia per riattivare la risposta inefficiente del linfocita T CD8+ nei confronti dell’HBV, sulla base del rilascio epatocellulare di interleuchina 2 (IL-2) da parte di vettori lentivirali. L’approccio con terapia genica fungerà da cura funzionale contro l’epatite B cronica attivando il sistema immunitario contro il virus.
Obiettivo
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.
Campo scientifico
Programma(i)
Meccanismo di finanziamento
ERC-POC-LS - ERC Proof of Concept Lump Sum PilotIstituzione ospitante
20132 Milano
Italia