Cytokine traps: multi-component, high-affinity blockers of cytokine action
Cytokine traps: multi-component, high-affinity blockers of cytokine action
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DOI：
10.1038/nm811
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发表时间：
2003-01-01
期刊：
影响因子：
82.9
通讯作者：
Stahl, N
中科院分区：
文献类型：
--
作者：
Economides, AN;Carpenter, LR;Stahl, N
细胞因子可以引发和延续人类疾病，并且是最有效的治疗靶点之一。细胞因子可以通过使用可溶性受体来阻断;然而，对于使用多组分受体系统的细胞因子如白介素（IL）-1，IL-4，IL-6和IL-13，使用这种方法是有限的，因为单体可溶性受体通常表现出低亲和力或作为激动剂的功能。我们在这里描述了一种普遍适用的方法，以创建非常高的亲和力阻断剂，称为'细胞因子陷阱'的IgG的恒定区和两个不同的细胞因子受体成分参与结合细胞因子的细胞外结构域之间的融合组成。Traps在体外和体内有效地阻断细胞因子，代表了在创造新的治疗候选药物用于治疗尼古丁驱动的疾病方面的实质性进展。
Cytokines can initiate and perpetuate human diseases, and are among the best-validated of therapeutic targets. Cytokines can be blocked by the use of soluble receptors; however, the use of this approach for cytokines such as interleukin (IL)-1, IL-4, IL-6 and IL-13 that use multi-component receptor systems is limited because monomeric soluble receptors generally exhibit low affinity or function as agonists. We describe here a generally applicable method to create very high-affinity blockers called 'cytokine traps' consisting of fusions between the constant region of IgG and the extracellular domains of two distinct cytokine receptor components involved in binding the cytokine. Traps potently block cytokines in vitro and in vivo and represent a substantial advance in creating novel therapeutic candidates for cytokine-driven diseases.