Emerging monoclonal antibodies as targeted innovative therapeutic approaches to asthma.
Asthma is characterized by discordant responses among cells of the adaptive and innate immune systems. This interplay involves a complex pattern of cytokine-driven processes resulting in cell migration and recruitment, inflammation, and proliferative states. The significant majority of asthmatic patients respond well to conventional inhaled treatments. However, about 5% of asthmatics have severe refractory asthma and account for 50% of the health expenditure on asthma. Human(ized) monoclonal antibodies (hMabs) targeting inflammatory pathways are promising therapeutic agents in asthma management. The anti-IgE hMab omalizumab was the first biologic treatment approved for the treatment of allergic asthma. Potential future strategies and targets include interleukin (IL)-5, IL-4, and IL-13, anti-TSLP, IL-25, and IL-33. hMabs targeting IL-5 have shown great promise in severe refractory asthma with a persisting eosinophilia, and clinical trials with hMabs against IL-13 and IL4Rα have also shown clinical benefit. Studies of hMabs against other cytokines in severe asthma are under way.
Firestone Institute of Respiratory Health and the Department of Medicine, Michael G DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
P D
PD
Mitchell
Firestone Institute of Respiratory Health and the Department of Medicine, Michael G DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
A I
AI
El-Gammal
Firestone Institute of Respiratory Health and the Department of Medicine, Michael G DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
P M
PM
O'Byrne
D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D018448:Models, Immunological; D058990:Molecular Targeted Therapy / Q000379:methods*
D061067:Antibodies, Monoclonal, Humanized; D018836:Inflammation Mediators