Albumin fusion improves the pharmacokinetics and in vivo antitumor efficacy of canine interferon gamma.

ABSTRACT

Interferon (IFN)-γ plays an important role in antiviral, anti-proliferative, immunomodulatory and pro-inflammatory activities. However, the short therapeutic half-life of IFN-γ lessens its efficacy. Albumin fusion strategy is one of the most effective ways to improve the pharmacokinetic properties of cytokines. In this study, N- and C-terminal canine albumin fusions with canine IFN-γ were expressed in the baculovirus expression system. The fusion proteins stimulated Stat1 phosphorylation at levels similar to that of the recombinant IFN. The antiviral, anti-proliferative and promote apoptosis activity of CSA-IFN-γ was lower than IFN-γ-CSA and both were less than that of recombinant IFN-γ. In vivo pharmacokinetics demonstrated a significantly longer half-life for CSA-IFN-γ (21.73 h) than for IFN-γ-CSA (6.51 h) and canine reIFN-γ (2.22 h) in Wistar rats. CSA-IFN-γ was also more effective than IFN-γ-CSA and canine reIFN-γ at inhibiting growth of canine renal malignant histiocytosis in nude mice. Our results indicated that a canine serum albumin fusion at the N-terminus of IFN-γ prolongs its half-life and improves its in vivo antitumor activity.