A MONOCLONAL ANTI-HUMAN IL-6 RECEPTOR ANTIBODY INHIBITS THE PROLIFERATION OF HUMAN MYELOMA CELLS
A MONOCLONAL ANTI-HUMAN IL-6 RECEPTOR ANTIBODY INHIBITS THE PROLIFERATION OF HUMAN MYELOMA CELLS
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DOI：
10.1089/hyb.1993.12.621
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发表时间：
1993-10-01
期刊：
影响因子：
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通讯作者：
VITETTA, ES
中科院分区：
文献类型：
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作者：
HUANG, YW;VITETTA, ES
通过用转染 hIL-6R cDNA 的人骨髓瘤细胞系 (U266) 和鼠细胞系 (M12.4/R) 免疫 BALB/c 小鼠，产生针对人 IL-6 受体 (hIL-6R) 的单克隆抗体 (UV4)。 流式细胞分析表明，UV 4 可对 hIL-6R+ 细胞系 U266 和 U937 进行染色，但不会对 hIL-6R- 细胞系 Daudi 和 K562 进行染色。竞争性抑制测定表明，U266 细胞与 UV4 预孵育可抑制藻红蛋白 (PE)-IL-6 缀合物与 hIL-6R 的结合，并抑制 IL-6 在 IL-6 依赖性人骨髓瘤细胞系 ILKM2 和 ILKM3 上的增殖活性。相反，UV4不干扰hIL-6R-伯基特淋巴瘤细胞系Daudi的增殖。直接夹心放射免疫测定进一步证实UV4与山羊抗hIL-6R抗体结合至同一分子。这些结果表明 UV4 和人 IL-6 均与 hIL-6R 上相同或相邻的表位结合。这种单克隆抗体应该有助于研究 IL-6R 的结构-功能关系，并可能有助于治疗多发性骨髓瘤等 IL-6 依赖性疾病。
A monoclonal antibody (UV4) against the human IL-6 receptor (hIL-6R) was generated by immunizing BALB/c mice with both a human myeloma cell line (U266) and a murine cell line (M12.4/R) transfected with the hIL-6R cDNA. Flow cytometric analysis demonstrated that UV 4 stains the hIL-6R+ cell lines U266 and U937, but not the hIL-6R- cell lines Daudi and K562. Competitive inhibition assays demonstrated that preincubation of U266 cells with UV4 inhibited the binding of a phycoerythrin (PE)-IL-6 conjugate to the hIL-6R and also inhibited the proliferative activity of IL-6 on the IL-6-dependent human myeloma cell lines ILKM2 and ILKM3. In contrast, UV4 did not interfere with the proliferation of the hIL-6R- Burkitt's lymphoma cell line, Daudi. Direct sandwich radioimmunoassays further confirmed that the UV4 bound to the same molecule as the goat anti-hIL-6R antibody. These results suggest that both UV4 and human IL-6 bind to the same or adjacent epitopes on the hIL-6R. This monoclonal antibody should facilitate studies of the structure-function relationship of IL-6R and may be useful for the treatment of IL-6-dependent diseases such as multiple myeloma.