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Distinct Clinical and Laboratory Activity of Two Recombinant Interleukin-2 Preparations¹

Departments of Human Oncology [J. A. H., J. S., J. G., P. M. S.], Pediatrics [P. M. S.], Genetics [P. M. S.], and Medicine [M. A., J. H. S., K. M. H., M. K.], and the Comprehensive Cancer Center [J. A. H., M. A., M. L., J. H. S., P. M. S.], University of Wisconsin, Madison, Wisconsin 53792

Interleukin-2 (IL-2) is a potent lymphokine that activates natural killer cells, T cells, and other cells of the immune system. Several distinct recombinant human IL-2 preparations have shown antitumor activity, particularly for renal cell cancer and melanoma. Somewhat distinct immune and clinical effects have been noted when different IL-2 preparations have been tested clinically; however, the regimens and doses used were not identical. To compare these more directly, we have evaluated two clinical recombinant IL-2 preparations in vitro and in vivo using similar regimens and similar IUs of IL-2. We used the Food and Drug Administration-approved, commercially available 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 differences 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 induced the release of more soluble IL-2 receptor into the serum than Chiron IL-2. In addition, more toxicities were noted in patients receiving 1.5 x 10⁶ IU of HLR IL-2 than were seen in patients treated with 1.5 x 10⁶ or even 4.5 x 10⁶ IU of Chiron IL-2. These toxicities included fever, nausea 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 incorporation. Using flow cytometry, we also found quantitative differences in the ability of these two preparations to bind to IL-2 receptors. These findings indicate that 3–6 IU of Chiron IL-2 are required to induce the same biological effect as 1 IU of HLR IL-2.

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