Harb Hani, Chatila Talal A
Division of Immunology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Clin Exp Allergy. 2020 Jan;50(1):5-14. doi: 10.1111/cea.13491. Epub 2019 Sep 30.
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.
Th2细胞因子白细胞介素4(IL-4)和IL-13以及它们与之相互作用的异二聚体白细胞介素4受体(IL-4R)复合物在过敏性疾病的发病机制中起关键作用。度普利尤单抗是一种人源化IgG4单克隆抗体,靶向IL-4R复合物(1型:IL-4Rα/γc;对IL-4具有特异性;2型:IL-4Rα/IL-13Rα1;对IL-4和IL-13具有特异性)共有的IL-4受体α链(IL-4Rα)。在本综述中,我们详细阐述了与IL-4R复合物相关的不同信号通路的当前知识状态,研究了度普利尤单抗的可能作用机制,并探讨了其在不同过敏性疾病中的临床疗效。度普利尤单抗的研发及其临床应用范围的扩大与当前对过敏性疾病相关通路阻断的精准医学方法的重视相关。