The biologic activity and molecular characterization of a novel synthetic interferon-alpha species, consensus interferon.
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.
Blatt
L M
LM
Amgen Inc., Thousand Oaks, CA 91230, USA.
Davis
J M
JM
Klein
S B
SB
Taylor
M W
MW
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D016384:Consensus Sequence; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000628:therapy; D011994:Recombinant Proteins; D017386:Sequence Homology, Amino Acid
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins