Kato Atsuhiko, Watanabe Takeshi, Yamazaki Masaki, Deki Toshiaki, Suzuki Masami
Safety Assessment Department, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
Regul Toxicol Pharmacol. 2009 Feb;53(1):46-51. doi: 10.1016/j.yrtph.2008.10.007. Epub 2008 Oct 30.
Interleukin-6 (IL-6) is a pleiotropic cytokine and a contributing factor in many diseases such as rheumatoid arthritis, Castleman's disease, Crohn's disease, and multiple myeloma. Since the blockade of the signaling pathway of the IL-6/interleukin-6 receptor (IL-6R)/gp130 complex is considered to have therapeutic value in such diseases, we developed an IL-6R humanized antibody (tocilizumab). In the current report, distribution of IL-6R in both normal human and cynomolgus monkey tissues was assessed as fundamental data to support preclinical and clinical studies of tocilizumab. Human and cynomolgus monkey tissue panels were stained with commercially available anti-human IL-6R and a species- and isotype-matched negative antibody, as well as assay control slides. The detection system applied used an Envision immunoperoxidase staining procedure with DAB reaction. Positive reactions were observed in the tissue elements of lymphatic, hematopoietic, digestive, reproductive, exocrine, endocrine, neural, muscular, epidermal, respiratory, and urinary systems of the human and cynomolgus monkey tissue panels. The current report is inclusive of a wide variety of tissues and shows the distribution of IL-6R to be similar for both human and monkey tissues. We consider this information fundamental for the support and interpretation of preclinical and clinical studies of anti-IL-6R antibody therapy.
白细胞介素-6（IL-6）是一种多效性细胞因子，在许多疾病中起作用，如类风湿性关节炎、卡斯特曼病、克罗恩病和多发性骨髓瘤。由于阻断IL-6/白细胞介素-6受体（IL-6R）/gp130复合物的信号通路被认为在此类疾病中具有治疗价值，我们研发了一种IL-6R人源化抗体（托珠单抗）。在本报告中，评估了IL-6R在正常人和食蟹猴组织中的分布情况，作为支持托珠单抗临床前和临床研究的基础数据。用人和食蟹猴组织切片与市售抗人IL-6R抗体、物种和亚型匹配的阴性抗体以及检测对照玻片进行染色。所应用的检测系统采用DAB反应的Envision免疫过氧化物酶染色程序。在人和食蟹猴组织切片的淋巴、造血、消化、生殖、外分泌、内分泌、神经、肌肉、表皮、呼吸和泌尿系统的组织成分中观察到阳性反应。本报告涵盖了多种组织，并显示IL-6R在人和猴组织中的分布相似。我们认为这些信息对于支持和解释抗IL-6R抗体治疗的临床前和临床研究至关重要。
