Project description
Gene therapy for chronic hepatitis
The hepatitis B virus (HBV) can cause cirrhosis and hepatocellular carcinoma, leading to one million deaths per year worldwide. Since the mechanisms underlying HBV persistence are poorly understood, there is no definitive cure, and current treatments aim to reduce the development of liver disease. The EU-funded 2LIVEr project is working on a novel strategy to reactivate the ineffective CD8+ T cell response towards the HBV based on the hepatocellular delivery of interleukin-2 (IL-2) by lentiviral vectors. This gene therapy approach will serve as a functional cure against chronic hepatitis B by activating the immune system against the virus.
Objective
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.
Fields of science
Programme(s)
Funding Scheme
ERC-POC-LS - ERC Proof of Concept Lump Sum PilotHost institution
20132 Milano
Italy