A Bivalent Immunoadhesin of the Human Interferon-γ Receptor Is an Effective Inhibitor of IFN-γ Activity

Abstract

We describe here the bioengineering of a bivalent IFN-γ-RFc immunoadhesin consisting of the extracellular domain of the human IFN-γ receptor α chain (IFN-γ-R) fused to a human IgG₁ Fc region (encoding hinge, CH2 and CH3 domain) that was efficiently expressed as a covalently linked homodimer in insect cells and purified in a one-step purification procedure. The IFN-γ-RFc fusion protein exerted a 3-fold higher ligand binding affinity in binding competition studies in vitro compared with the monovalent extracellular IFN-γ-R domain. In addition, the in vitro antagonistic activity of IFN-γ-RFc, as determined by inhibition of IFN-γ-induced virus protection and HLA-DR expression, was more than 30-fold higher in comparison with the monovalent soluble receptor. The described IFN-γ-R immunadhesin is a potential therapeutic reagent to interfere with the disease-promoting activities of IFN-γ in several autoimmune diseases.