Effects of recombinant interferon-alpha on immune function in cancer patients

Patients with a variety of malignancies were treated in phase I clinical trials of recombinant leukocyte A interferon (IFL-rA) schedules consisting of either twice-daily doses for 28 days (48 patients) or three times weekly for 28 days (86 patients). Extensive monitoring of several immune functions was done on these patients, with rigorously standardized assays and determination of inherent variability of function for each individual. The assays performed were natural killer (NK) cell cytotoxicity, monocyte cytostatic activity, lymphoproliferative responses to concanavalin A (con A) and mixed leukocyte culture, and an analysis of changes in leukocyte populations as determined using a panel of monoclonal antibodies and flow cytometry. No appreciable increase in NK activity was observed on any of the treatment regimens, and an unexpected observation was the depression of activity in a substantial proportion (30%) of patients. In contrast, monocyte function, as measured in an assay of growth inhibition of tumor target cells, was found to be elevated in 70% of the patients. Lymphoproliferative responses were depressed in most patients in response to both con A and the mixed leukocyte culture. Cell surface marker studies revealed an increase in the percentage of OKT10 positive cells in the majority of patients studied and a transient increase in cells reacting with the antibody MO2. The data have been analyzed in terms of their relationship to dose and schedule of administration, and the depression of NK activity was shown to be greatest at the highest doses and more frequent schedule of administration.