IL-6 functions in cynomolgus monkeys blocked by a humanized antibody to human IL-6 receptor.
A humanized antibody to the human interleukin-6 receptor (IL-6R), hPM-1, blocked the interleukin-6 (IL-6) functions in normal cynomolgus monkey lymphocytes in vitro. The binding activity of hPM-1 to non-human primate IL-6R was examined in peripheral blood lymphocytes by flow cytometry. PM-1 recognized the IL-6R on T lymphocytes of cynomolgus and rhesus monkeys, but did not on those of marmosets. The homology between human IL-6R and its cynomolgus monkey counterpart was 97.3% in the extracellular domain of the amino acid sequence, as determined by DNA sequencing of the PCR product from peripheral blood mononuclear cells. PM-1 inhibited two functional parameters in vitro in cynomolgus monkeys: (1), T-cell proliferation stimulated by phytohemaglutinin and human IL-6; (2), Immunoglobulin G-production evoked by Staphylococcus aureus Cowan-1- and human IL-6-stimulated B lymphocytes. These data show that hPM-1 binds to and functionally blocks the cynomolgus monkey IL-6 receptors.
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, Tokyo, Japan.
I
I
Imazeki
H
H
Saito
M
M
Hasegawa
H
H
Shinkura
T
T
Kishimoto
Y
Y
Ohsugi
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D001483:Base Sequence; D002144:Callithrix; D002478:Cells, Cultured; D003429:Cross Reactions; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D015850:Interleukin-6 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000187:drug effects; D008252:Macaca fascicularis / Q000276:immunology*; D008253:Macaca mulatta; D051379:Mice; D008969:Molecular Sequence Data; D010835:Phytohemagglutinins / Q000494:pharmacology; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity; D013211:Staphylococcus aureus / Q000276:immunology
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015850:Interleukin-6; D010835:Phytohemagglutinins; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins