In Vivo Administration of Purified Human Interleukin-2 to Patients with Cancer: Development of Interleukin-2 Receptor Positive Cells and Circulating Soluble Interleukin-2 Receptors following Interleukin-2 Administration

Michael T. Lotze, Susan O. Sharrow, Laurence A. Rubin, David L. Nelson, Steven A. Rosenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Recent studies have demonstrated efficacy of immunotherapies including interleukin-2 (IL-2) in the treatment of malignancies in rodents and humans. High levels of IL-2 receptor-positive cells were found in the peripheral blood of patients receiving recombinant IL-2 in these Phase I clinical trials. This was demonstrated both in patients receiving i.v. IL-2 who had detectable circulating levels of IL-2 as well as in patients receiving i.p. IL-2 who did not. Up to 100% of the anti-Tac binding could be inhibited by preincubation with IL-2 indicating that this was indeed an IL-2 receptor that was identified. Two-color experiments demonstrated that few Leu 2-positive cells (<5-10%) but over 30% of the Leu 3-positive cells bore Tac antigen. Most of the M3-positive monocytes were Tac positive (83.7%) and negative for other T-cell (Leu-4) and nonspecific murine markers (Lyt-2 and Thy 1.2). Although normal individuals had a mean of only 186 units/ml (range, 83–335 units/ml) of soluble IL-2 receptor, patients receiving IL-2 had as much as 20, 000 units/ml of soluble IL-2 receptor line in their serum. The physiological role of the IL-2 receptor identified on the cell surface of Leu 3 and M3-positive cells as well as in the serum is unclear. Soluble IL-2 receptors appeared in the circulation early following IL-2 administration, approximately 1 week prior to the detection of circulating IL-2 receptor-bearing cells. Further studies will be needed to assess the role of IL-2 in monocyte function, the precise function of IL-2 receptor-bearing Leu 3-positive cells, and the relationship of these findings to the toxicity and success of this immunotherapy in humans.

Original languageEnglish (US)
Pages (from-to)2188-2195
Number of pages8
JournalCancer Research
Volume47
Issue number8
StatePublished - Apr 1987

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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