Imazeki I, Saito H, Hasegawa M, Shinkura H, Kishimoto T, Ohsugi Y
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, Tokyo, Japan.
Int J Immunopharmacol. 1998 Jul;20(7):345-57. doi: 10.1016/s0192-0561(98)00005-8.
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.
一种针对人白细胞介素-6受体（IL-6R）的人源化抗体hPM-1，在体外可阻断正常食蟹猴淋巴细胞中的白细胞介素-6（IL-6）功能。通过流式细胞术在外周血淋巴细胞中检测了hPM-1与非人灵长类动物IL-6R的结合活性。PM-1可识别食蟹猴和恒河猴T淋巴细胞上的IL-6R，但不能识别狨猴T淋巴细胞上的IL-6R。通过对外周血单个核细胞PCR产物进行DNA测序确定，人IL-6R与其食蟹猴对应物在氨基酸序列的细胞外结构域中的同源性为97.3%。PM-1在体外可抑制食蟹猴的两个功能参数：（1）由植物血凝素和人IL-6刺激的T细胞增殖；（2）由金黄色葡萄球菌Cowan-1和人IL-6刺激的B淋巴细胞诱发的免疫球蛋白G产生。这些数据表明，hPM-1可结合并在功能上阻断食蟹猴IL-6受体。
