Recombinant antibodies against viral interleukin-6
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.