Directed evolution of broadly crossreactive chemokine-blocking antibodies efficacious in arthritis
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; ... Show more Show less
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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.
DepartmentMassachusetts 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
Nature Publishing Group
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
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