人源化抗人TNF-α单克隆抗体在转基因小鼠体内的药效学实验  

The in vivo pharmacodynamics reserch of humanization anti-human TNF-α monoclonal antibody in transgene mouse

作　　者：袁杰 吴英良[1] 苏冬梅[2] 

机构地区：[1]沈阳药科大学生命科学和生物制药学院,辽宁沈阳110016 [2]沈阳三生制药有限责任公司,辽宁沈阳110027

出　　处：《沈阳药科大学学报》2018年第2期138-144,共7页Journal of Shenyang Pharmaceutical University

摘　　要：目的研究人源化抗人肿瘤坏死因子-α单克隆抗体(recombinant humanization anti-human tumor necrosis factorαmonoclonal antibody,rhTNF-McAb)对人TNF-α转基因小鼠自发性关节炎的治疗作用。方法以市售药物Adalimumab为阳性药物,通过给予不同剂量的rhTNF-McAb对转基因小鼠的自发性足肿胀度、小鼠四肢综合肌力和踝关节组织病理学变化,用ELISA法检测小鼠体内人TNF-α质量浓度、血药质量浓度和抗药物抗体质量浓度。结果rhTNF-McAb(0.5 mg·kg^(-1),1.5 mg·kg^(-1),4.5 mg·kg^(-1))腹腔给药对人TNF-α转基因小鼠的自发性足肿胀有显著的治疗作用,并呈现明显的剂量依赖性关系,作用机制与阳性药物Adalimumab一致。但rhTNF-McAb在小鼠体内的清除情况,产生抗药物抗体的滴度与Adalimumab明显不同。结论rhTNF-McAb可以显著的抑制人TNF-α,并且其疗效更优于已上市类似药物Adalimumab。Objective To study the protective effect of humanized anti-human TNF-α monoclonal antibody （rhTNF-McAb） on spontaneous arthritis of human TNF-α transgene mouse. Methods After injecting the positive drug adalimumab and different doses of rhTNF-McAb, the idiopathic paw swelling, muscular strength and ankle joint histopathology of transgene mouse were observed. ELISA assays were performed to determine human TNF-α concentration, blood drug concentration and anti-drug antibodies concentration. Results The intraperitoneal injection （i. p. ） of rhTNF-McAb （0. 5 mg·kg^-1 ,1.5 mg·kg^-1 ,4.5 mg·kg^-1 ） significantly and dose-dependently inhibited idiopathic paw swelling in human TNF-α transgene mouse, and the action mechanism of rhTNF-McAb was same with that of adalimumab. However, the drug clearance, an- ti-drug antibodies concentration of rhTNF-McAb were different from that of adalimumab. Conclusions The results suggest that rhTNF-McAb significantly inhibited human TNF-α and the therapeutic effect of rhTNF- McAb was better than that of adalimumab.

关 键 词：人源化抗人肿瘤坏死因子-α单克隆抗体 人肿瘤坏死因子-α转基因小鼠 药效学 

分 类 号：R96[医药卫生—药理学]