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-Interferons: 40th Anniversary of the Discovery of Interferons1
Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee 38163 [L. M. P.]; Department of Medicine, University of Colorado Health Science Center, Division of Infectious Diseases, Denver, Colorado 80262 [C. A. D.]; Departments of Medicine and Pathology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213 [R. B. H.]; Department of Cancer Biology, Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195 [B. R. G. W.]; University of Maryland School of Medicine Cancer Center, Baltimore, Maryland 21201 [E. C. B.]; Schering-Plough Research Institute, Kenilworth, New Jersey 07033 [R. B.]; Department of Pharmacology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005 [M. R. W.]; Canji, Inc., San Diego, California 92121 [T. L. N.]; Applied Clinical Communications, Inc., Parsippany, New Jersey 07054 [P. P. T.]; and Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635 [S. P.]
IFNs were first described as potent antiviral agents 40 years ago, and recombinant IFN-
2a and IFN-2b were approved for the treatment of hairy cell leukemia just 11 years ago. Today, -IFNs are approved worldwide for the treatment of a variety of malignancies and virologic diseases. Although the exact mechanism of action of IFN- 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-, the nature of the multisubunit IFN- receptor, and the molecular mechanisms of signal transduction. Where available, we have included comparative data on recombinant -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 -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- and thus deliver new applications for this prototypic cytokine, whose full therapeutic potential is yet to be realized.
1 The contents of this article reflect data presented at a closed round table meeting entitled "Recombinant -IFNs from Naturally Occurring Genes: The Gold Standard Continues," held in Tucson, Arizona from January 17–19, 1997. The meeting and preparation of this article were supported by an unrestricted educational grant from Schering Oncology/Biotech, a division of Schering-Plough Corporation. A portion of the text represents work that was performed by C. A. D. and supported in part by NIH Grant AI-15614.
2 To whom requests for reprints should be addressed, at Department of Pathology, University of Tennessee Health Science Center, 899 Madison Avenue, Memphis, TN 38163. Phone: (901) 448-5362.
Received 11/ 5/97. Accepted 4/21/98.
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