The interferons: Past, present and future

From their discovery in 1957, the characterization and development of interferons (IFNs) as major biotherapeutic products has been a continuing enterprise for over 50 years. The IFNs have featured in pioneering fundamental research that has uncovered countless facets of their structural and biological properties. A great deal has been learned too about the induction and mechanisms of action of interferons, this knowledge being translated into their development as potent therapeutic agents. While they proved of limited success in the clinic against malignant tumours, great progress has been made in establishing IFN-α as the first choice of treatment for chronic hepatitis C virus (HCV) infections and, surprisingly, IFN-β for relapsing remitting multiple sclerosis. Biological standardization has enabled IFN products to be measured in meaningful units of biological activity, thus ensuring consistency of production and dose administration to patients. Within the last 10 years, development of novel pegylated IFN-α2 products with extended in vivo half-lives has dramatically improved treatment regimes for HCV patients. Undesirable side effects and immunogenicity of therapeutic IFN products remain obstacles to overcome for further improvements in clinical applications. It is confidently expected that research in the IFN field will continue, not only to face these immediate challenges but also to extend the range of IFN products and clinical targets.