A PHASE-I STUDY OF PROLONGED CONTINUOUS-INFUSION OF LOW-DOSE RECOMBINANT INTERLEUKIN-2 IN MELANOMA AND RENAL-CELL CANCER .2. IMMUNOLOGICAL ASPECTS

Previously we described the clinical aspects of a phase I study of pro longed continuous infusion of low-dose recombinant interleukin-2 (rIL- 2). In the present paper we report several immunological effects in 13 patients with melanoma and renal cell cancer treated on an out-patien t basis with rIL-2 for uninterrupted periods ranging from 5 to 18 week s. Groups of three patients were treated at following dose levels 0.18 , 0.6, 1.8 or 6 x 10(6) IU m-2 24 h-1 and one patient was treated with 3 x 10(6) IU m-2 24 h-1. Prolonged rIL-2 treatment resulted in a dose -dependent and sustained increase in the percentage and absolute numbe r of (CD56+, CD8dim) natural killer cells. Within this population a pr eferential increase in the CD56bright cells with low expression of CD1 6 was observed. The CD27 antigen was also upregulated in the CD56(brig ht)CD16dim population. This increase of NK cells was accompanied by an enhancement of the cytotoxic capacity of the peripheral lymphocytes. No consistent signs of T cell activation or expansion were noted.