This paper describes our experience in the production, stabilization, and clinical application of mouse interferon. The interferons are species-specific, low molecular weight proteins elaborated by living cells in response to viral or other induction.' When the interferons made by these cells are applied to other cells of the same species, they inhibit or annul both viral propagation and viral transformation.2 Interferon protects cells against a wide variety of viruses; the prophylactic efficacy has been demonstrated often. We have found additionally, however, that interferon has an even broader area of competence. This paper presents evidence that interferon is a carcinolytic agent capable of destroying cells that have already been transformed by some earlier event. The therapeutic promise of interferon thus takes on a new dimension.The fulfillment of this promise depends not only on the demonstration of clinical efficacy, but also on the feasibility of producing interferon in useful amounts. Interferon is yielded by living cells both in vivo and in vitro. It appears at peak levels in the body fluids within a few hours after the administration of an interferogen to the animal, and then declines to nought within a few days. Repetitive administration of the inducer, even were it not prohibitively toxic, as it often is, is only negligibly productive. Cells in vitro respond similarly, are restricted to one cycle of interferon production, and cannot be used again. The difficulties, or anticipated difficulties, of growing enough cells in inducible state for tangible exogenous production has disinclined most laboratories from undertaking the venture. These laboratories turned instead to what appeared to be a more promising approach, a search for safe and effective interferogens. We, however, elected to produce interferon in vitro.The requirements for the production of interferon are simply stated: a supply of viable cells of the species desired; any interferogen to which these cells will respond, toxicity being of but little moment; methods for the isolation, concentration, and stabilization of the product; and a method for assay. We prepared interferon from L-929 mouse fibroblasts propagated in large-scale suspension culture systems. The inducer was live egg-grown Newcastle disease virus.
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