Dissertation (Metadaten)
Titel:Recombinant antibodies against viral interleukin-6
 
Autor:Marina Kovaleva
 
URN:NBN:urn:nbn:de:gbv:8-diss-12999
 
Fakultät:Mathematisch-Naturwissenschaftliche Fakultät
DDC Sachgebiet:610 Medizin und Gesundheit
 
Datum der mdl. Prüfung:15.12.2004
 
Referent(in):Prof. Dr. Stefan Rose-John
Korreferent(en) Korreferentin:Prof. Dr. Matthias leippe
 
Beschreibung:The genome of KaposisÕs sarcoma associated herpesvirus, encodes several ORFs for putative oncogenes, which are homologues to cellular host genes. One of these genes encodes viral interleukin-6 (vIL-6). The viral cytokine is believed to play an important role in the pathogenesis of KaposiÕs sarcoma as well as PEL, multicentic CastelmanÕs disease and perhaps multiple myeloma. Therefore, vIL-6 is a promising target for novel therapies directed against HHV-8-associated diseases. In this study a recombinant antibody (scFv) against vIL-6 was screened from a phage display human antibody library. vIL-6 was demonstrated to be specifically recognised by this antibody (called MAV). MAV binds to recombinant vIL-6 immobilised on a solid phase and to the native cytokine in solution. MAV was shown to inhibit vIL-6-induced signaling in human hepatoma cells. Based on the idea to block vIL-6 secretion, a strategy for the neutralisation of vIL-6 was developed and tested. The recombinant antibody MAV was fused with the endoplasmicretention sequence KDEL (MAV-KDEL) to be retained in the endoplasmic reticulum. As a result, cells secreting vIL-6 ceased to secrete the cytokine after transfection with MAV-KDEL.
 
Schlagworte:viral interleukin-6, antibodies, scFv, Kaposi's sarcoma associated herpesvirus
 
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