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-α2a and IFN-α2b, 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-α. In contrast, consensus interferon was shown to be an inferior inducer of IL-1β when compared with IFN-α. 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.