Enhanced Circulation Half-life for Human IFNα2b and IgG Fc Fusion Protein

Abstract:

Recombinant human interferon alpha (rHuIFNα) has been successfully used in antiviral and antitumor treatment. However, it degrades rapidly in vivo, resulting in the disappearance of cytokine in the plasma within several hours after administration. Strategies including chemical modification and fusion proteins have been used to improve the half-life of IFNα in vivo. In the present study, we constructed fusion proteins with IFNα2b and the IgG Fc region from various subtypes of human IgG and expressed them in methylotropic yeast, Pichia pastries. The fusion proteins were secreted to the culture medium as the active form of disulfide-linked homodimer with a single glycoslation modification on each molecule. Regardless of the subtype of Fcγ, fusing Fcγ fragments to IFNα2b showed impaired antiviral activities than the control IFNa2b in vitro. With the highest antiviral activity, IFNα2b-Fcγ2 was measured as 4.29×107 IU/mg, which decreased 2.3 times compared to the control IFNa2b. The half-life of IFNα2b-Fcγ2 in blood circulation extended to 65 hours and was still detectable until 120 hours, which was 8 times longer for circulation half-life and 10 times longer for metabolic kinetic time than the control IFNα2b. The results demonstrated that fusing IgG Fc region with IFNα2b could improve the pharmacokinetic properties of the fusion proteins, which has the potential in clinical therapy.