Biological monitoring of low-dose interleukin 2 in humans: soluble interleukin 2 receptors, cytokines, and cell surface phenotypes.
Different immunotherapy regimens using s.c. recombinant interleukin-2 (rIL-2) were studied in 76 patients with progressive metastatic renal carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, or Hodgkin's disease. To assess the immunomodulatory capacity of rIL-2, we measured serum levels of soluble interleukin-2 (sIL-2) receptors, gamma-interferon, tumor necrosis factor-alpha, and various lymphocyte subsets expressing the CD25 Tac IL-2 receptor and the CD56 natural killer (NK) associated antigen. Additionally, we measured serum antibodies specific to rIL-2 in order to evaluate immunogenicity of rIL-2. In all patients, a significant increase in sIL-2 receptor levels could be observed when comparing values on day 0 and after one treatment course. Patients developing a neutralizing anti-rIL-2 antibody exhibited significantly lower serum sIL-2 receptor levels than patients without antibody. Soluble IL-2 receptors correlated with the percentage of CD25 IL-2 receptor-positive peripheral blood lymphocytes. Both soluble and cell surface IL-2 receptors exhibited a significant increase during rIL-2 therapy but did not correlate with the percentage of CD56-positive peripheral blood lymphocytes. Measurement of treatment-induced secondary cytokines showed significant increases in gamma-interferon serum levels in a proportion of patients tested, although with considerable interindividual variability. No significant increase in mean tumor necrosis factor-alpha levels was observed during rIL-2 treatment in vivo. The percentage of CD56-positive NK cells correlated with the clinical outcome of rIL-2 therapy. Thus, partial or complete responders had an increase from a mean of 20% NK cells prior to therapy up to a mean of 40% after the first treatment course. In contrast, patients with progressive disease had a mean of 22 and 24% NK cells before and after treatment, respectively.
Department of Hematology and Oncology, Medizinische Hochschule Hanover, Germany.
E L
EL
Hänninen
A
A
Körfer
M
M
Hadam
C
C
Schneekloth
I
I
Dallmann
T
T
Menzel
H
H
Kirchner
H
H
Poliwoda
J
J
Atzpodien
D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy; D006689:Hodgkin Disease / Q000276:immunology / Q000628:therapy; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000032:analysis* / Q000097:blood; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy; D007694:Killer Cells, Natural / Q000737:chemistry* / Q000276:immunology; D008214:Lymphocytes / Q000737:chemistry; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy; D008545:Melanoma / Q000276:immunology / Q000628:therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma