From bench to bedside - Inhaled Interleukin-13 antibody: preliminary results from an animal model of asthma
Interleukin (IL)-13 plays a central role in the pathogenesis of asthma. Following exposure to the allergen, Th2 lymphocytes release large amounts of IL-13 in the airways resulting in mucus overproduction, secretion of inflammatory cytokines and B-cell stimulation to produce IgE.
This year the results of three trials performed in patients with asthma with monoclonal antibodies against IL-13administered subcutaneously (lebrikizumab and tralokinumab) were published. No effect on pulmonary function (Korenblat P 2018), number of eosinophils in airways, blood and sputum (Russell RJ 2018) or exacerbation rate (Panettieri RA Jr 2018) was reported. However, a significant reduction in FeNO and total IgE was demonstrated (Russell RJ 2018).
The study published in the last number of the Blue Journal (Lightwood D 2018) reports for the first time the results of a nebulized inhaled anti-interleukin-13 monoclonal antibody Fab fragment in an animal model of allergic asthma. The antibody was nebulized using eFlow technology in macaques sensitized to Ascaris suum and significantly inhibited the production of cytokines (IL-4, IL-5, IL-8, IFNg) and chemokines in BAL and the increase in pulmonary resistance. No adverse effects were reported. As highlighted by the authors, the inhalation of anti-IL-13 offers many potential advantages: a therapeutic action localized into the lung, the reduction of systemic exposure and side effects, the non-invasive administration.
These preclinical data support further studies in human patients.
Korenblat P, Kerwin E, Leshchenko I, Yen K, Holweg CTJ, Anzures-Cabrera J, Martin C, Putnam WS, Governale L, Olsson J, Matthews JG. Efficacy and safety of lebrikizumab in adult patients with mild-to-moderate asthma not receiving inhaled corticosteroids. Respir Med. 2018 Jan;134:143-149.
Russell RJ, Chachi L, FitzGerald JM, Backer V, Olivenstein R, Titlestad IL, Ulrik CS, Harrison T, Singh D, Chaudhuri R, Leaker B, McGarvey L, Siddiqui S, Wang M, Braddock M, Nordenmark LH, Cohen D, Parikh H, Colice G, Brightling CE; MESOS study investigators. Effect of tralokinumab, an interleukin-13 neutralising monoclonal antibody, on eosinophilic airway inflammation in uncontrolled moderate-to-severe asthma (MESOS): a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. Lancet Respir Med. 2018 May 18. pii: S2213-2600(18)30201-7.
Panettieri RA Jr, Sjöbring U, Péterffy A, Wessman P, Bowen K, Piper E, Colice G, Brightling CE. Tralokinumab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trials. Lancet Respir Med. 2018 May 18. pii: S2213-2600(18)30184-X.
Lightwood D, Tservistas M, Zehentleitner M, Sarkar K, Turner A, Bracher M, Smith B, Lamour S, Bourne T, Shaw S, Gozzard N, Palframan RT. Efficacy of an Inhaled Interleukin-13 Antibody Fragment in a Model of Chronic Asthma. Am J Respir Crit Care Med. 2018 Jun 8.