The Kennedy Institute Division, Faculty of Medicine, Imperial College School of Medicine, 65 Aspenlea Road, London W6 8LH, United Kingdom.
Curr Opin Pharmacol. 2010 Jun;10(3):308-15. doi: 10.1016/j.coph.2010.01.005. Epub 2010 Feb 19.
Tumor necrosis factor-alpha (TNF) has been unequivocally validated as a therapeutic target in a number of immune-mediated inflammatory disorders (IMIDs). There is now increasing choice of biologic agents within the class all of which successfully neutralize sTNF. But approaches to TNF inhibition differ and currently include mAbs (infliximab, adalimumab, and golimumab), either chimeric or human in sequence, a PEGylated Fab' fragment (certolizumab), and an IgG1-TNFR2 fusion protein (etanercept). It is emerging that the pharmacological properties of these three anti-TNF subtypes differ with respect to Fc function, binding of tmTNF and the possible consequences of this, as well as the ability to form complexes. The mode of administration of each agent, clearance and the local tissue concentrations achieved may also confer unique characteristics of relevance with respect to efficacy and safety.
肿瘤坏死因子-α（TNF）已被明确验证为多种免疫介导的炎症性疾病（IMIDs）的治疗靶点。目前，该类生物制剂的选择越来越多，所有这些制剂都能成功中和可溶性 TNF。但是，TNF 抑制的方法不同，目前包括 mAb（英夫利昔单抗、阿达木单抗和戈利木单抗），要么是嵌合的，要么是序列上的人源化，一种 PEGylated Fab'片段（培塞利珠单抗），以及一种 IgG1-TNFR2 融合蛋白（依那西普）。目前看来，这三种抗 TNF 亚型的药理学特性在 Fc 功能、tmTNF 的结合及其可能产生的后果以及形成复合物的能力方面存在差异。每种药物的给药方式、清除率和达到的局部组织浓度也可能赋予与疗效和安全性相关的独特特征。
