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

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 1999

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Interleukin-2
Interleukin-2 Receptors
National Cancer Institute (U.S.)
Lymphokines
United States Food and Drug Administration
Renal Cell Carcinoma
Natural Killer Cells
Thymidine
Nausea
Vomiting
Immune System
Melanoma
Flow Cytometry
Fever
chiron

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

Distinct clinical and laboratory activity of two recombinant interleukin-2 preparations. / Hank, Jacquelyn A.; Surfus, Jean; Gan, Jacek; Albertini, Mark; Lindstrom, Mary; Schiller, Joan H.; Hotton, Kirsten M.; Khorsand, Masoud; Sondel, Paul M.

In: Clinical Cancer Research, Vol. 5, No. 2, 02.1999, p. 281-289.

Research output: Contribution to journalArticle

Hank, JA, Surfus, J, Gan, J, Albertini, M, Lindstrom, M, Schiller, JH, Hotton, KM, Khorsand, M & Sondel, PM 1999, 'Distinct clinical and laboratory activity of two recombinant interleukin-2 preparations', Clinical Cancer Research, vol. 5, no. 2, pp. 281-289.
Hank JA, Surfus J, Gan J, Albertini M, Lindstrom M, Schiller JH et al. Distinct clinical and laboratory activity of two recombinant interleukin-2 preparations. Clinical Cancer Research. 1999 Feb;5(2):281-289.
Hank, Jacquelyn A. ; Surfus, Jean ; Gan, Jacek ; Albertini, Mark ; Lindstrom, Mary ; Schiller, Joan H. ; Hotton, Kirsten M. ; Khorsand, Masoud ; Sondel, Paul M. / Distinct clinical and laboratory activity of two recombinant interleukin-2 preparations. In: Clinical Cancer Research. 1999 ; Vol. 5, No. 2. pp. 281-289.
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