Directed evolution of broadly crossreactive chemokine-blocking antibodies efficacious in arthritis
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Author(s)
Miyabe, Yoshishige
Miyabe, Chie
Luster, Andrew D.
Angelini, Alessandro
Newsted, Daniel
Kwan, Byron Hua
Kelly, Ryan Lewis
Jamy, Misha N.
Wittrup, Karl Dane
Date Issued
April 2018
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Angelini, Alessandro, et al. “Directed Evolution of Broadly Crossreactive Chemokine-Blocking Antibodies Efficacious in Arthritis.” Nature Communications, vol. 9, no. 1, Dec. 2018. © 2018 The Authors
Version
Final published version
Abstract
Chemokine receptors typically have multiple ligands. Consequently, treatment with a blocking antibody against a single chemokine is expected to be insufficient for efficacy. Here we show single-chain antibodies can be engineered for broad crossreactivity toward multiple human and mouse proinflammatory ELR+CXC chemokines. The engineered molecules recognize functional epitopes of ELR+CXC chemokines and inhibit neutrophil activation ex vivo. Furthermore, an albumin fusion of the most crossreactive single-chain antibody prevents and reverses inflammation in the K/BxN mouse model of arthritis. Thus, we report an approach for the molecular evolution and selection of broadly crossreactive antibodies towards a family of structurally related, yet sequence-diverse protein targets, with general implications for the development of novel therapeutics.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/s41467-018-03687-x
