BIOLOGICAL PROPERTIES OF RECOMBINANT ALPHA-INTERFERONS - 40TH ANNIVERSARY OF THE DISCOVERY OF INTERFERONS

IFNs were first described as potent antiviral agents 40 years ago, and recombinant IFN-alpha(2a) and LFN-alpha(2b) were approved for the tre atment of hairy cell leukemia just 11 years ago. Today, alpha-IFNs are approved worldwide for the treatment of a variety of malignancies and virologic diseases. Although the exact mechanism of action of IFN-alp ha in the treatment of such diseases is not fully understood, many adv ances have been made in the characterization of the physicochemical an d diverse biological properties of this highly pleiotropic cytokine, H ere we review recent developments in our understanding of the antivira l and immunoregulatory properties of IFN-alpha, the nature of the mult isubunit IFN-alpha receptor, and the molecular mechanisms of signal tr ansduction, Where available, we have included comparative data on reco mbinant alpha-IFNs derived from both naturally occurring and nonnatura lly occurring synthetic genes. We also review clinical data and data o n the side effects and antigenicity of different sources of recombinan t alpha-IFNs in humans. These latter topics are of clinical interest, because they may potentially affect the efficacy of these various prod ucts. Hopefully, what is already known about IFN will prompt further e xploration into the mechanism(s) of action of IFN-alpha and thus deliv er new applications for this prototypic cytokine, whose full therapeut ic potential is yet to be realized.