Towards tumor therapy with interferons, Part I. Interferons: production and properties.

I NTERFERONS are a family of inducible secretory glycoproteins produced by eukaryotic cells in response to viral infections or other stimuli. They are intercellular messages which, upon binding to specific cell surface receptors, direct cells to express a new, interferon-induced, phenotype. They have, therefore, aptly been called “inducible inducers.” Characteristically, all interferons induce in cells a resistance to a broad spectrum of viruses. This easily quantifiable effect is used to measure the biologic activity of interferon preparations.** Interferon production and action involve the workings of several structural and regulatory genes. These can be activated rapidly and their products detected within hours. Because of both its rapidity of action and its effectiveness, this “interferon system” is an important first line of defense against viral infections. In addition, it may protect against other intracellular parasites, and even against neoplastic transformation of cells and against tumor growth. The evidence that has led to these conclusions is the subject of these reviews. This first part deals with the production of interferons, their physicochemical properties, and their biologic activities. The following part will review the development of prophylaxis and therapy with interferons. The existence of “interferon” was discovered in 1957. Over the ensuing 22 yr. it was realized that there exists a number of different molecular forms of interferon all endowed with antiviral and other biologic properties. Various animal and human interferons have been obtained as progressively more punfled and potent preparations, and their effects on cells can now be studied at the molecular level, using preparations of apparent purity. Thus, it has recently been demonstrated that many of the effects obtained with impure preparations-including the inhibition of tumor growth in the mouse-can be attributed to the interferon molecules themselves. Although begun with still very impure preparations, clinical investigations with interferons are yielding encouraging results. Thus, interferons are of considerable scientific interest and also promising as prophylactic and therapeutic agents. There is ample justification for their large-scale production for further clinical testing, and for expansion and consolidation of the basis of knowledge needed to bring interferon therapy to rational, medical application.