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Human monoclonal antibody therapy to prevent hepatitis C virus reinfection of liver transplants: advancing lead monoclonal antibodies into clinical trial (HepaMAb)
Date du début: 1 janv. 2013, Date de fin: 31 déc. 2017 PROJET  TERMINÉ 

Worldwide, 200 million people are infected with the hepatitis C virus (HCV). An estimated 15 million individuals are living with HCV infection within the EU. The economic, health and societal costs of chronic HCV infection are significant. HCV is the principal cause of death from liver disease and the leading indication for liver transplantation. The only treatment for end-stage liver disease is a liver transplant, yet the transplanted liver becomes rapidly re-infected and is frequently destroyed within 5 years after transplantation. In this cohort of patients current antiviral treatments are too toxic - there is an urgent need to develop safe and effective treatments for use in this setting. Human monoclonal antibodies (MAbs) that target virus entry, are as yet an underutilised and potentially highly effective and safe weapon in the armoury against HCV infection. The consortium has identified MAb leads which, in pre-clinical analyses, potently block HCV infection. HCV exhibits a high degree of genetic and antigenic variability, which enables the virus to escape protective immune responses. Crucially, the lead antibodies identified by the consortium are capable of preventing infection by a wide range of genetically distinct isolates because they target highly conserved epitopes on the virus or host receptor molecules. This limits the chances of virus resistance. Also, each lead antibody targets a unique component of the viral entry pathway, thereby paving the way for powerful combinatorial approaches which maximises clinical potency. HepaMAb harnesses leading expertise in MAb technology, preclinical efficacy and safety testing, biomanufacture and clinical trial to progress at least one anti-viral and one anti-receptor human MAb to phase I/IIa proof of concept clinical trial in the liver transplant setting for the prevention of graft reinfection. We will establish a much-needed therapeutic MAb pipeline for use in this solid organ transplant setting.

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