Descripción del proyecto
La genoterapia para la hepatitis crónica
El virus de la hepatitis B (VHB) puede provocar cirrosis y carcinoma hepatocelular, lo que causa un millón de muertes cada año en todo el mundo. Dado que aún no se comprenden bien los mecanismos que subyacen a la persistencia del VHB, no existe una cura definitiva y los tratamientos actuales tienen como objetivo reducir el desarrollo de la enfermedad hepática. El proyecto 2LIVEr, financiado con fondos europeos, está trabajando en una nueva estrategia para reactivar la respuesta ineficaz de los linfocitos T citotóxicos frente al VHB basada en la liberación hepatocelular de interleucina-2 (IL-2) por vectores lentivíricos. Este enfoque de la genoterapia servirá como una cura funcional contra la hepatitis B crónica al activar el sistema inmunitario contra el virus.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-POC-LS - ERC Proof of Concept Lump Sum PilotInstitución de acogida
20132 Milano
Italia