Biological properties of recombinant α-interferons: 40th Anniversary of the discovery of interferons

Lawrence M. Pfeffer, Charles A. Dinarello, Ronald B. Herberman, Bryan R.G. Williams, Ernest C. Borden, Ronald Bordens, Mark R. Walter, Tattanahalli L. Nagabhushan, Paul P. Trotta, Sidney Pestka

Research output: Contribution to journalReview ArticleResearchpeer-review

461 Citations (Scopus)

Abstract

IFNs were first described as potent antiviral agents 40 years ago, and recombinant IFN-α(2a) and IFN-α(2b) were approved for the treatment of hairy cell leukemia just 11 years ago. Today, α-IFNs are approved worldwide for the treatment of a variety of malignancies and virologic diseases. Although the exact mechanism of action of IFN-α in the treatment of such diseases is not fully understood, many advances have been made in the characterization of the physicochemical and diverse biological properties of this highly pleiotropic cytokine. Here we review recent developments in our understanding of the antiviral and immunoregulatory properties of IFN-α, the nature of the multisubunit IFN-α receptor, and the molecular mechanisms of signal transduction. Where available, we have included comparative data on recombinant α-IFNs derived from both naturally occurring and nonnaturally occurring synthetic genes. We also review clinical data and data on the side effects and antigenicity of different sources of recombinant α-IFNs in humans. These latter topics are of clinical interest, because they may potentially affect the efficacy of these various products. Hopefully, what is already known about IFN will prompt further exploration into the mechanism(s) of action of IFN-α and thus deliver new applications for this prototypic cytokine, whose full therapeutic potential is yet to be realized.

Original languageEnglish
Pages (from-to)2489-2499
Number of pages11
JournalCancer Research
Volume58
Issue number12
Publication statusPublished - 15 Jun 1998
Externally publishedYes

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