Abstract

Monoclonal Antibody Therapy for the Management of Severe Asthma

Suzanne Cohen, , MedImmune

Asthma is a chronic inflammatory disorder of the airways characterized by inflammation, variable airflow obstruction and airways hyper responsiveness. It is estimated that asthma affects 5–10% of adults. In the majority, asthma can be controlled by inhaled corticosteroids and long acting beta-agonists. However, in ~5% of sufferers asthma remains severe despite standard of care and may require additional treatment with biological agents. Severe asthma involves a number of variants with different underlying pathologies. The recognition of the Th2 phenotype of severe asthma has facilitated the development of new biotherapeutics showing efficacy in subgroups of asthmatics. Anti-IL-5 mAbs have been recently approved. mAbs that inhibit the signalling of IL-4/IL-13 are in late stage development. However, it is not yet clear whether these drugs will effectively treat all subtypes of severe asthma. More recently Genome Wide Association Studies have consistently implicated epithelial cytokines TSLP and IL-33 in asthma. A crucial role for TSLP has been determined in human allergen challenge studies. IL-33 is yet to be validated in the clinic but emerging preclinical data indicate a fascinating and multifunctional role for this molecule as well as an intriguing biochemistry that has implications for antibody discovery.