title: Optimization of CAT-354, a therapeutic antibody directed against interleukin-13, using ribosome display.
abstract: In this case study, we describe the use of in vitro protein evolution with ribosome display to improve the potency of a human interleukin-13-neutralising antibody by a factor of over 200-fold and derive a therapeutic candidate, CAT-354, for the treatment of asthma. A combination of directed and random mutagenesis enabled the identification of highly potent neutralising antibodies and highlighted the advantage of the ribosome display protein evolution approach in identifying beneficial mutations across the entire sequence space. This chapter describes in detail the process followed to achieve a successful in vitro affinity maturation outcome using ribosome display technology.
authors.affiliation: Department of Antibody Discovery and Protein Engineering, MedImmune, Cambridge, UK.
authors.forename: George
authors.initials: G
authors.lastname: Thom
authors.forename: Ralph
authors.initials: R
authors.lastname: Minter
mesh_terms: D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000494:pharmacology; D000915:Antibody Affinity; D001249:Asthma / Q000188:drug therapy; D019020:Directed Molecular Evolution; D006801:Humans; D018793:Interleukin-13 / Q000037:antagonists & inhibitors* / Q000276:immunology*; D012270:Ribosomes / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D018793:Interleukin-13