Modulation of interferon-specific gene expression by albumin-interferon- α in interferon-α-experienced patients with chronic hepatitis C

Vijayan Balan, David R. Nelson, Mark S. Sulkowski, Gregory T. Everson, Louis R. Lambiase, Rusell H. Wiesner, Rolland C. Dickson, Andy Garcia, Paul A. Moore, Ren Yu, G. Mani Subramanian

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Albumin-interferon-α (alb-IFN) is a novel recombinant protein derived from IFN-α2b genetically fused to human albumin. The resulting single polypeptide combines in one molecule the antiviral properties of IFN-α with the long serum half-life of albumin. IFN-mediated biological responses stem from the engagement of IFN-α with its target receptor and subsequent modulation of IFN-specific gene (ISG) expression. To evaluate the pharmacodynamics of alb-IFN during the Phase I/II study conducted in patients with chronic hepatitis C (CHC) who had previously failed IFN-α-containing regimens, ISG induction was evaluated in peripheral blood and compared with antiviral response. Whole blood was obtained at day 0, day 7 and day 28 from 21 patients enrolled in the higher dose (500-900 μg) alb-IFN cohort, who received two injections on day O and day 14. Taqman real-time PCR was used to assess candidate ISG expression. There was sustained induction on day 7 and day 28 of the ISG's OAS1, IRF-7, IFI44 and IFI27. Although all patients showed a molecular response to alb-IFN, individual variability in pretreatment gene expression levels and fold of modulation during treatment was observed. At day 28, induction of OAS1, IFI44 and IRF7 showed pairwise correlation in individual patients (P<0.05). Moreover, the induction of expression at day 28, and pretreatment levels of OAS1 and IFI44 correlated with hepatitis C virus RNA reduction at day 28 (P<0.05). In conclusion, alb-IFN demonstrated robust induction of ISG that was consistent with the response associated with an IFN-α.

Original languageEnglish (US)
Pages (from-to)901-908
Number of pages8
JournalAntiviral Therapy
Volume11
Issue number7
StatePublished - Nov 17 2006

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Modulation of interferon-specific gene expression by albumin-interferon- α in interferon-α-experienced patients with chronic hepatitis C'. Together they form a unique fingerprint.

Cite this