- Genovac GmbH
- Waltershofener Str. 17
- 79111 Freiburg
- Stefan Lang
- +49 (761) 45636-16
GENOVAC and Inserm co-develop a novel antibody-based approach for prevention and treatment of chronic hepatitis C
Due to the growing number of infected HCV patients resistant to current antiviral therapy, the total therapeutic market is expected to grow from a current 3-5 billion USD / year to 5-10 billion USD over the next 10 years.
A major problem for the development of effective antiviral therapies lays in the biology of the virus. This is a socalled RNA virus which is prone to mutation during the formation of new viruses in the liver cells. Such mutations rapidly occur in patients and lead to new infective forms of the virus that become resistant to therapy. To infect the liver the virus requires socalled receptor proteins or entry factors, present on the surface of the liver cells, to which it attaches and thus gains entry to the cell, where it can start to divide and produce new viruses. New viruses can then infect neighbouring liver cells, leading to spread of the disease. The approach adopted by GENOVAC in Freiburg, Germany, and Inserm U748 in Strasbourg, France, is to generate antibodies that specifically bind to claudin-1 - a key HCV entry factor on the surface of the liver cells, thus blocking viral entry and infection of the liver cells. Unlike the mutating virus, these receptor proteins do not mutate but are used by all viral variants to gain cell entry. GENOVAC and Inserm have successfully generated monoclonal antibodies (i.e., cloned antibodyproducing cells, which can be cultivated in cell culture indefinitely) of a given specificity for claudin-1 and two other HCV receptor proteins. All of these block infection of human liver cells in cell culture. Furthermore, they show broad blocking efficiency to all mutant variants of HCV including variants which escape the patient's immune responses.
The antibodies are now further developed to protect and treat HCV infection in patients. The antibodies could be applied to protect transplanted livers from chronic HCV infection. Investigations in animal models are underway to assess the possibility of treating chronically infected HCV patients.
"Thus far, attempts to generate antibodies against the extracellular loop structures on the HCV receptor proteins have proven unsuccessful. By applying our unique genetic immunisation technology, we have now been successful in generating antibodies that not only recognise the native receptors on the surface of human liver cells, but actively block HCV entry for three different receptors" says Dr John Thompson, Managing Director, GENOVAC GmbH.
"This approach clearly holds major promise for prevention of HCV infection in transplantation and widens the therapeutic arsenal against HCV infection" says Thomas Baumert, Professor of Medicine and principal investigator of the functional studies which is published in this month's issue of the journal Gastroenterology (Fofana I. et al 2010, Gastoenterology 139(3):953-964). A joint patent has been filed by GENOVAC, Inserm and the University of Strasbourg on these antibodies (WO2010034812).
Inserm U748, University of Strasbourg (www.u748.inserm.fr):
Inserm is the only French public research body entirely dedicated to human health. Its researchers are committed to studying all diseases, whether common or rare, through their research in the fields of biology, medicine and public health (www.inserm.fr). Aiming at the understanding of the pathogenesis of HCV infection and the development of novel antivirals, the Inserm unit 748 is headed by Prof. Thomas Baumert, MD, and focuses on the identification of the molecular mechanisms of HCVhost interactions. Innovative, stateoftheart approaches in molecular virology and biology, immunology, functional genomics and clinical hepatology are applied to identify viral and host mechanisms mediating viral persistence and pathogenesis of infection. The impact of these findings is studied in novel cell culture and animal models, and in clinical trials with HCVinfected patients.
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