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Article
Nature Medicine 9, 47 - 52 (2002)
Published online: 16 December 2002 | doi:10.1038/nm811
Cytokine traps: multi-component, high-affinity blockers of cytokine action
Aris N. Economides1,8, Laura Rocco Carpenter1,8, John S. Rudge1, Vivien Wong2, Ellen M. Koehler-Stec2, Christopher Hartnett3, Erica A. Pyles3, Xiaobing Xu3, Thomas J. Daly3, Michael R. Young4, James P. Fandl4, Frank Lee5, Scott Carver5, Jennifer McNay5, Kevin Bailey5, Swayampakula Ramakanth6, Renta Hutabarat6, Tammy T. Huang7, Czeslaw Radziejewski7, George D. Yancopoulos1 & Neil Stahl1
Abstract
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.
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