Effect of recombinant alpha interferon on NK and ADCC function in lung cancer patients: results from a phase II trial.

Abstract

During a phase II trial of recombinant IFN-alpha given in doses of 50 X 10(6) units/m2 three times per week to lung cancer patients, 13 patients were evaluated longitudinally in NK and ADCC assays and in immunofluorescence tests enumerating the number of cells reactive with the new N901 NK-cell antibody. An increase in NK-cell activity could be demonstrated when values before and 24 h after the first injection of IFN were compared, but simultaneously the enhancing effect of IFN-alpha on NK-cells added to in vitro cultures was abolished, probably as a result of preactivation of NK cells in vivo. After 2-4 weeks of treatment, the majority of patients exhibited a pronounced decrease in NK-cell activity while still retaining the inability to be boosted by IFN added in vitro. Investigations with the NK antibody N901 showed that the initial increase in NK activity appeared concomitantly with an increase in the number of N901 positive cells, indicating that the mechanism behind this increase was an increase in the number of circulating NK cells. In contrast, the decrease in NK activity mentioned above was not followed by a similar decrease in the number of N901+ cells, and it was concluded that this decrease might be attributable to either an exhaustion phenomenon or to an induction of a refractory state of peripheral blood NK cells. When measuring ADCC activity, increases in lytic activity were seen only in patients in whom they could be attributed to non-IgG-dependent (NK-like) mechanisms. These data are discussed in relation to other clinical trials using leukocyte or recombinant IFN-alpha.