Mechanisms of Dupilumab

Abstract

The Th2 cytokines interleukin 4 (IL-4) and IL-13 and the heterodimeric IL-4 receptor (IL-4R) complexes that they interact with play a key role in the pathogenesis of allergic disorders. Dupilumab is a humanized IgG4 monoclonal antibody that targets the IL-4 receptor alpha chain (IL-4Rα), common to both IL-4R complexes: type 1 (IL-4Rα/γc; IL-4 specific) and type 2 (IL-4Rα/IL-13Rα1; IL-4 and IL-13 specific). In this review, we detail the current state of knowledge of the different signalling pathways coupled to the IL-4R complexes and examine the possible mechanisms of Dupilumab action and survey its clinical efficacy in different allergic disorders. The development of Dupilumab and the widening spectrum of its clinical applications is relevant to the current emphasis on precision medicine approaches to the blockade of pathways involved in allergic diseases.

Keywords: IL-4R; T cells; T-reg; asthma; atopic dermatitis; dupilumab; food allergy.