Distinct clinical and laboratory activity of two recombinant interleukin-2preparations

Interleukin-2 (IL-2) is a potent lymphokine that activates natural killer c ells, T cells, and other cells of the immune system. Several distinct recom binant human IL-2 preparations have shown antitumor activity, particularly for renal cell cancer and melanoma, Somewhat distinct immune and clinical e ffects have been noted when different IL-2 preparations have been tested cl inically; however, the regimens and doses used were not identical. To compa re these more directly, we have evaluated two clinical recombinant IL-2 pre parations in vitro and in vivo using similar regimens and similar IUs of IL -2, We used the Food and Drug Administration-approved, commercially availab le Chiron IL-2 and the Hoffmann LaRoche (HLR) IL-2 supplied by the National Cancer Institute. Using equivalent IUs of IL-2, we noted quantitative diff erences in vitro and in vivo in the IL-2 activity of these two preparations , In patients receiving comparable IUs of the two preparations, HLR IL-2 in duced the release of more soluble IL-2 receptor cr into the serum than Chir on IL-2, In addition, more toxicities were noted in patients receiving 1.5 x 10(6) IU of HLR IL-2 than were seen in patients treated with 1.5 x 10(6) or even 4.5 x 10(6) IU of Chiron IL-2, These toxicities included fever, nau sea and vomiting, and hepatic toxicity. In vitro proliferative assays using IL-2-dependent human and murine cell Lines indicated that the IU of HLR IL -2 was more effective than Chiron IL-2 at inducing tritiated thymidine inco rporation. Using flow cytometry, we also found quantitative differences in the ability of these two preparations to bind to IL-2 receptors, These find ings indicate that similar to 3-6 IU of Chiron IL-2 are required to induce the same biological effect as 1 IU of HLR IL-2.