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Benralizumab: A New Approach for the Treatment of Severe Eosinophilic Asthma

Dávila González I1, Moreno Benítez F2, Quirce S3

1Allergy Service, University Hospital of Salamanca, School of Medicine, University of Salamanca, Salamanca, Spain
2Immunology and Allergy Unit, Clínica Lobatón, Cádiz, Spain; Grupo Asociado AS03 Inmunología y Alergia, associated with IN-CO16 INIBICA (Instituto Biomédico de Cádiz), Cádiz, Spain
3Department of Allergy, Hospital Universitario La Paz Institute for Health Research (IdiPAZ) and CIBER of Respiratory Diseases (CIBERES), Madrid, Spain

J Investig Allergol Clin Immunol 2019; Vol 29(2) : 84-93
doi: 10.18176/jiaci.0385

Eosinophilic asthma is the most common phenotype of severe asthma. It is characterized by abnormal production and release of type 2 cytokines from T helper type 2 (TH2) lymphocytes and type 2 innate lymphoid cells, such as IL-5. This leads to a persistent increase and activation of eosinophils in blood and the airways despite treatment with high-dose inhaled corticosteroids. Eosinophil differentiation, survival, and activation are preferentially regulated by IL-5, a cytokine that binds to the IL-5 receptor (IL-5R), which is located on the surface of eosinophils or basophils and plays a critical role in the pathogenesis and severity of asthma. Benralizumab is a monoclonal antibody that binds to IL-5R via its Fab domain, blocking the binding of IL-5 to its receptor and resulting in inhibition of eosinophil differentiation and maturation in bone marrow. In addition, this antibody is able to bind through its afucosylated Fc domain to the RIIIa region of the Fcy receptor on NK cells, macrophages, and neutrophils, thus strongly inducing antibody-dependent, cell-mediated cytotoxicity in both circulating and tissue-resident eosinophils. This double function of benralizumab induces almost complete fast and maintained depletion of eosinophils that is much greater than that induced by other monoclonal antibodies targeting the IL-5 pathway, such as mepolizumab and reslizumab. This review focuses on benralizumab as an alternative to other agents targeting the IL-5 pathway in the treatment of eosinophilic asthma.

Key words: Eosinophils, Basophils, ILC-2, Exacerbations, Phenotype