Tezepelumab: A Potential New Biological Therapy for Severe Refractory Asthma.

Alessandro Vatrella,Rosa Terracciano,Luca Gallelli,Giulia Pelaia,Angelantonio Maglio,Corrado Pelaia,Claudia Crimi

doi:10.3390/ijms22094369

Abstract

Thymic stromal lymphopoietin (TSLP) is an innate cytokine, belonging to the group of alarmins, which plays a key pathogenic role in asthma by acting as an upstream activator of cellular and molecular pathways leading to type 2 (T2-high) airway inflammation. Released from airway epithelial cells upon tissue damage induced by several noxious agents including allergens, viruses, bacteria, and airborne pollutants, TSLP activates dendritic cells and group 2 innate lymphoid cells involved in the pathobiology of T2-high asthma. Tezepelumab is a fully human monoclonal antibody that binds to TSLP, thereby preventing its interaction with the TSLP receptor complex. Preliminary results of randomized clinical trials suggest that tezepelumab is characterized by a good safety and efficacy profile in patients with severe, uncontrolled asthma.

Highlights

Asthma is a chronic obstructive respiratory disease, mainly characterized by airflow limitation due to bronchial inflammation and airway remodeling [1,2]
A key pathophysiologic role is played by thymic stromal lymphopoietin (TSLP), an innate cytokine especially involved in type 2 eosinophilic inflammation, and implicated in neutrophilic and paucigranulocytic asthma [15,16,17]
In addition to being implicated in the pathobiology of type 2 airway inflammation, Thymic stromal lymphopoietin (TSLP) appears to be involved in type 2” (T2)-low neutrophilic asthma, characterized by a pivotal pathogenic role played by Th17 lymphocytes [71]

Summary

Introduction

Asthma is a chronic obstructive respiratory disease, mainly characterized by airflow limitation due to bronchial inflammation and airway remodeling [1,2]. In addition to chronic inflammation, all asthma endotypes are often characterized by airway structural changes, which span throughout the various layers of the bronchial wall [11] These remodeling features include goblet cell metaplasia/hyperplasia, subepithelial fibrosis sustained by activation of fibroblasts and myofibroblasts, smooth muscle thickening, and neo-angiogenesis [11]. In T2-high asthma, the development, persistence, and amplification of eosinophilic inflammation are driven and orchestrated by multiple cellular elements including dendritic cells, T helper 2 (Th2) lymphocytes, group 2 innate lymphoid cells (ILC2), mast cells, basophils, and airway epithelial cells [12,13,14] Within this endotypic context, a key pathophysiologic role is played by thymic stromal lymphopoietin (TSLP), an innate cytokine especially involved in type 2 eosinophilic inflammation, and implicated in neutrophilic and paucigranulocytic asthma [15,16,17]. In light of the above considerations, this article aims to review the role of TSLP in asthma pathophysiology, as well as to discuss the therapeutic properties of tezepelumab as an eventual add-on treatment option for severe asthma

Pathogenic Role of TSLP in Asthma

Tezepelumab

Findings

Conclusions