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

Jacquelyn A. Hank, Jean Surfus, Jacek Gan, Mark Albertini, Mary Lindstrom, Joan H. Schiller, Kirsten M. Hotton, Masoud Khorsand, Paul M. Sondel

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20 Scopus citations

Abstract

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 !L-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 α 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/L-2. These toxicities included fever, nausea and vomiting, and hepatic toxicity. In vitro proliferative assays using !L-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.

Original languageEnglish (US)
Pages (from-to)281-289
Number of pages9
JournalClinical Cancer Research
Volume5
Issue number2
StatePublished - Feb 1 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hank, J. A., Surfus, J., Gan, J., Albertini, M., Lindstrom, M., Schiller, J. H., Hotton, K. M., Khorsand, M., & Sondel, P. M. (1999). Distinct clinical and laboratory activity of two recombinant interleukin-2 preparations. Clinical Cancer Research, 5(2), 281-289.