The biologic activity and molecular characterization of a novel synthetic interferon-alpha species, consensus interferon

• Published in: Journal of interferon & cytokine research Vol. 16; no. 7; p. 489
• Main Authors: Blatt, L M, Davis, J M, Klein, S B, Taylor, M W
• Format: Journal Article
• Language: English
• Published: United States 01-07-1996
• Subjects: Amino Acid Sequence; Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Consensus Sequence; Drug Screening Assays, Antitumor; Humans; Interferon Type I - pharmacology; Interferon-alpha; Molecular Sequence Data; Neoplasms, Experimental - therapy; Recombinant Proteins; Sequence Homology, Amino Acid
• ISSN: 1079-9907
• DOI: 10.1089/jir.1996.16.489

Consensus interferon (Infergen) is a wholly synthetic type I interferon (IFN), developed by scanning several interferon-alpha nonallelic subtypes and assigning the most frequently observed amino acid in each position, resulting in a consensus sequence. The antiviral, antiproliferative, NK cell activation activity, cytokine induction, and interferon-stimulated gene-induction activity of consensus interferon has been compared with naturally occurring type I interferons. In all of these comparisons, consensus interferon had a higher activity when compared, on a mass basis, with IFN-alpha 2a and IFN-alpha 2b, although the activity was the same for all of these parameters on an antiviral unit basis. That a synthetic type I interferon could have higher activities than naturally occurring molecules is surprising and may be a result of the higher affinity for the array of type I interferon receptors demonstrated for consensus interferon when compared with IFN-alpha. In contrast, consensus interferon was shown to be an inferior inducer of IL-1 beta when compared with IFN-alpha. These results may reflect differential binding to multiple accessory proteins interacting with a type I interferon receptor. These unique biologic properties may lead to a favorable clinical benefit for consensus interferon when compared with the naturally occurring recombinant molecules. Ongoing clinical trials will ascertain whether consensus interferon can be used in a wide array of disease situations, such as chronic viral infections and certain malignancies.