Albumin fusion improves the pharmacokinetics and in vivo antitumor efficacy of canine interferon gamma
Autor: | Zou Shuzhan, Wu Jiajun, Chen Ruiai, Man-Lin Luo, Anni Chen, He-Xing Wang, Bing Li |
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Rok vydání: | 2019 |
Předmět: |
Recombinant Fusion Proteins
Serum albumin Mice Nude Pharmaceutical Science Antineoplastic Agents Apoptosis 02 engineering and technology Pharmacology 030226 pharmacology & pharmacy Interferon-gamma 03 medical and health sciences 0302 clinical medicine Pharmacokinetics In vivo Interferon Neoplasms medicine Animals Interferon gamma Rats Wistar Serum Albumin Cell Proliferation Mice Inbred BALB C biology Chemistry Albumin 021001 nanoscience & nanotechnology Fusion protein biology.protein Female 0210 nano-technology medicine.drug |
Zdroj: | International Journal of Pharmaceutics. 558:404-412 |
ISSN: | 0378-5173 |
Popis: | 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. |
Databáze: | OpenAIRE |
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