Preclinical biology of alpha interferons.

The availability of large quantities of purified recombinant human alpha interferons has permitted an expansion of studies on the preclinical biology of interferon. These purified preparations have definitively established that interferon exhibits pleiotypic effects on cellular function, including antiviral, antiproliferative, and immunomodulatory activities. Thus, interferon can exert therapeutic activity by both direct effects on the growth of the tumor and by modulation of the biologic response of the host. The exact mechanism of action will most probably vary from patient to patient. The variety of biologic activities that interferon displays, as well as the fact that it is highly species-specific, makes it difficult to design preclinical studies that can provide guidance for the clinical application of interferon as an antineoplastic agent. Two models that have provided useful preclinical data on human cell lines or fresh biopsies are reviewed: the human tumor clonogenic assay and human tumor xenografts in immunodeficient mice. These models indicate that interferon is likely to be an effective treatment for a broad range of malignancies, and that the response will be highly dependent on the type of interferon as well as its dose, schedule, and route of administration. Both models have provided evidence that alpha interferon may demonstrate a synergistic or additive interaction with standard chemotherapeutic agents like cyclophosphamide or doxorubicin. The utility of any preclinical model for predicting an individual patient's response to interferon is yet to be established.