MODULATION OF NK AND MONOCYTE ACTIVITY IN ADVANCED CANCER PATIENTS RECEIVING INTERFERON

134 patients with a variety of malignancies were treated in two Phase 1 clinical trials of recombinant leukocyte A interferon (IFN) produced by recombinant DNA methodology by Hoffmann-La Roche Inc. in collaboration with Genentech Inc. IFN was given either twice daily or three times weekly for 28 days. Extensive monitoring of immune function was done on these patients, in an attempt to define the range of doses of interferon and timing of administration that would optimally alter immune functions which might have beneficial anti-tumor effects. These two protocols failed to result in an appreciable increase in NK activity but rather in the majority of patients there was no significant change in NK activity from the pretreatment baseline levels. A particularly unexpected finding was the depresssion in NK activity seen in 30% of the patients. In contrast, the IFN preparation did induce significant augmentation of monocyte function, as measured in a monocyte-mediated cytostatic assay, with increases observed in 80% of the patients. There is some evidence for the presence of a suppressor factor in the sera of these patients which interfered with in vitro boosting of NK activity by IFN and therefore might have been responsible for the paradoxical NK results. These data have also been analyzed in terms of their possible relationship to doses, and protocol of IFN administration, and to tumor response.