| Autor: |
Sung, Cynthia, Nardelli, Bernardetta, LaFleur, David W., Blatter, Erich, Corcoran, Marta, Olsen, Henrik S., Birse, Charles E., Pickeral, Oxana K., Zhang, Junli, Shah, Devanshi, Moody, Gordon, Gentz, Solange, Beebe, Lisa, Moore, Paul A. |
| Zdroj: |
Journal of Interferon & Cytokine Research; January 01, 2003, Vol. 23 Issue: 1 p25-36, 12p |
| Abstrakt: |
The long half-life and stability of human serum albumin (HSA) make it an attractive candidate for fusion to short-lived therapeutic proteins. Albuferon™ (Human Genome Sciences [HGS], Inc., Rockville, MD) beta is a novel recombinant protein derived from a gene fusion of interferon-β (IFN-β ) and HSA. In vitro, Albuferon beta displays antiviral and antiproliferative activities and triggers the IFN-stimulated response element (ISRE) signal transduction pathway. Array analysis of 5694 independent genes in Daudi-treated cells revealed that Albuferon beta and IFN-β induce the expression of an identical set of 30 genes, including 9 previously not identified. In rhesus monkeys administered a dose of 50 μg/kg intravenously (i.v.) or subcutaneously (s.c.) or 300 μg/kg s.c., Albuferon beta demonstrated favorable pharmacokinetic properties. Subcutaneous bioavailability was 87%, plasma clearance at 4.7-5.7 ml/h/kg was approximately 140-fold lower than that of IFN-β, and the terminal half-life was 36-40 h compared with 8 h for IFN-β. Importantly, Albuferon beta induced sustained increases in serum neopterin levels and 2′,5′ mRNA expression. At a molar dose equivalent to one-half the dose of IFN-β, Albuferon beta elicited comparable neopterin responses and significantly higher 2′,5′-OAS mRNA levels in rhesus monkeys. The enhanced in vivo pharmacologic properties of IFN-β when fused to serum albumin suggest a clinical opportunity for improved IFN-β therapy. |
| Databáze: |
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