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.
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 (less than 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.
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects; D009369:Neoplasms / Q000032:analysis / Q000628:therapy*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000032:analysis*; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins / Q000627:therapeutic use; D012995:Solubility; D013601:T-Lymphocytes / Q000187:drug effects; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7