Cytokine traps: multi-component, high-affinity blockers of cytokine action

Author:  ["Aris N. Economides","Laura Rocco Carpenter","John S. Rudge","Vivien Wong","Ellen M. Koehler-Stec","Christopher Hartnett","Erica A. Pyles","Xiaobing Xu","Thomas J. Daly","Michael R. Young","James P. Fandl","Frank Lee","Scott Carver","Jennifer McNay","Kevin Bailey","Swayampakula Ramakanth","Renta Hutabarat","Tammy T. Huang","Czeslaw Radziejewski","George D. Yancopoulos","Neil Stahl"]

Publication:  Nature Medicine

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Tags:     Medicine

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.

Cite this article

Economides, A., Carpenter, L., Rudge, J. et al. Cytokine traps: multi-component, high-affinity blockers of cytokine action. Nat Med 9, 47–52 (2003). https://doi.org/10.1038/nm811

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