Projektbeschreibung
Gentherapie für chronische Hepatitis
Das Hepatitis-B-Virus (HBV) kann Zirrhosen und hepatozelluläre Karzinome verursachen, die weltweit pro Jahr zu einer Millionen Todesfällen führen. Da die Mechanismen, die der Beharrlichkeit des HBV zugrunde liegen, kaum verstanden werden, gibt es kein definitives Heilmittel, und aktuelle Behandlungen zielen darauf ab, die Entwicklung von Lebererkrankungen zu mindern. Das EU-finanzierte Projekt 2LIVEr arbeitet an einer neuartigen Strategie zur Reaktivierung der ineffektiven Reaktion der T-Zelle CD8+ auf das HBV, die auf der hepatozellulären Verabreichung von Interleukin-2 (IL-2) durch lentivirale Vektoren basiert. Dieser Gentherapieansatz wird als funktionales Heilmittel gegen chronische Hepatitis B dienen, indem das Immunsystem gegen das Virus aktiviert wird.
Ziel
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.
Wissenschaftliches Gebiet
Programm/Programme
Finanzierungsplan
ERC-POC-LS - ERC Proof of Concept Lump Sum PilotGastgebende Einrichtung
20132 Milano
Italien