Angelini, AlessandroMiyabe, YoshishigeNewsted, DanielKwan, Byron H.Miyabe, ChieKelly, Ryan L.Jamy, Misha N.Luster, AndrewWittrup, K. Dane2018-05-302018Angelini, Alessandro, Yoshishige Miyabe, Daniel Newsted, Byron H. Kwan, Chie Miyabe, Ryan L. Kelly, Misha N. Jamy, Andrew D. Luster, and K. Dane Wittrup. 2018. “Directed evolution of broadly crossreactive chemokine-blocking antibodies efficacious in arthritis.” Nature Communications 9 (1): 1461. doi:10.1038/s41467-018-03687-x. http://dx.doi.org/10.1038/s41467-018-03687-x.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37068013Chemokine 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.en-USJournal Article2018-05-3010.1038/s41467-018-03687-x