title: Engineering approaches to develop the next generation of antibodies to respiratory targets.
abstract: Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) represent a significant health burden worldwide and are a major unmet medical need. Asthma affects over 300 million people and leads to 250,000 deaths per year, with an increasing prevalence particularly in developing countries. Although a large proportion of asthmatics are maintained on beta agonists and corticosteroids, there still remains a group of patients where these medicines fail to modulate symptoms and who may therefore benefit from monoclonal antibody based drugs that are aimed at controlling the disease. COPD is a cigarette smoke-driven chronic inflammatory airway disease with an increasing global prevalence. Given that current therapies fail to prevent disease progression or mortality, this patient population is also a focus for the development of monoclonal antibody therapies. At present anti-IgE (omalizumab, Xolair®) is the only monoclonal antibody based drug approved in the respiratory space for the treatment of asthma. However, an increasing number of antibodies targeting key mediators/pathways of disease are in clinical development for both asthma and COPD, including targeting the Th2 pathway for asthma (anti-IL-4/5/13) and the pro-inflammatory cytokine IL-1 for COPD. This review will examine the antibody engineering approaches used to develop the next generation of antibodies, with a focus on respiratory disease.
authors.affiliation: Department of Antibody Discovery and Protein Engineering, MedImmune, Milstein Building, Granta Park, Cambridge, CB21 6GH, UK.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Vousden
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Clarke
authors.forename: David C
authors.initials: DC
authors.lastname: Lowe
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry* / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; C026408:anti-IgE antibodies