Monoclonal Antibodies for the Treatment of Severe Asthma

Abstract

Patients with severe asthma have a significant unmet need with persistent symptoms and/or frequent exacerbations despite treatment with high-dose steroid and other currently available therapies. These patients are also at risk of developing steroid-related side effects, and their severe, unrelenting symptoms have a huge impact on health care resources due to frequent hospital admissions and requirement for intensive medication use. Consequently, a compelling need exists for more effective and safer pharmacotherapies to help them achieve adequate disease control. Recent novel therapies for severe asthma are now emerging, some of the most promising of which are monoclonal antibodies. Monoclonal antibodies represent a form of immunotherapy used in a wide variety of therapeutic roles. The spectrum of disease states in which monoclonal antibodies have been approved for therapeutic use now includes respiratory and allergic diseases. At present, only one drug is licensed for allergic asthmatics with severe disease, omalizumab. We review some of the currently available biologics that are approved or under investigation for use in severe asthma. Some have shown to be useful in specifically targeted subpopulations of patients with severe asthma, whereas other have proven to be unsafe and/or unsuccessful. Despite these developments, more effort should be devoted to identifying new molecular targets, testing innovative approaches, and establishing the best use of what is available. Regarding this latter point, identifying individual characteristics that predict successful responses to these treatments is highly desirable.

Equine lung decellularization: a potential approach for in vitro modeling the role of the extracellular matrix in asthma

“…However, it is important to note that some therapeutic strategies for asthma previously derived from animal models in mice and rats have been failed when translated to human. 2 – 4 A reason explaining this deceiving result is differential different transcriptional responses to acute inflammatory in rodents and humans. 5 Interestingly, horses naturally develop an asthma-like condition currently known as recurrent airway obstruction (RAO), severe equine asthma, 6 and inflammatory airway disease (IAD), a mild-to-moderate asthma.…”

Asthma “of horses and men”—How can equine heaves help us better understand human asthma immunopathology and its functional consequences?

“…It is undoubted that mice models have helped uncovering novel immunological mechanisms responsible for the development of different disease processes. Nevertheless, therapeutic strategies derived from these studies have been for the most part disappointing when translated to human diseases, including asthma (Clienti et al, 2011;Giembycz and Newton, 2011;Nair et al, 2012). This may be in part due to different transcriptional responses to acute inflammatory insults in mice and men (Seok et al, 2013).…”

Epitope Mapping of a 95 kDa Antigen in Complex with Antibody by Solution-Phase Amide Backbone Hydrogen/Deuterium Exchange Monitored by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

“…Characterization of interaction/contact regions between protein antigens (i.e., epitopes) and antibodies is essential for understanding the mechanisms of antibody generation and immune recognition as well as basic aspects of protein–protein interactions. Clinical applications of such information include the rational design of vaccines and efforts to predict the biochemical motifs common to allergenic proteins. , The rapidly growing list of therapeutic of monoclonal antibodies (mAbs) also stimulates research on epitope characterization. − …”