Anti-TSLP antibodies: Targeting a master regulator of type 2 immune responses

Nakajima, Saeko; Kabata, Hiroki; Kabashima, Kenji; Asano, Koichiro

doi:10.1016/j.alit.2020.01.001

Cited by 67 publications

(56 citation statements)

References 83 publications

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“…We propose a concept of “adult‐onset eosinophilic airway diseases” including asthma, N‐ERD, ABPA/ABPM, CRSwNP/eosinophilic CRS, and EGPA. Common pathophysiology such as EETosis/mucus plug formation and common genetic backgrounds including TSLP/IL‐33 pathway genes seem to underlie these diseases 153,154 . In addition, each disease exhibits a specific pathophysiology such as mast cell and platelet activation in N‐ERD, fungal sensitization in ABPA/ABPM, abnormality in coagulation/fibrinolysis pathway in CRSwNP/eosinophilic CRS and autoimmunity in EGPA.…”

Section: Resultsmentioning

confidence: 99%

“…Common pathophysiology such as EETosis/ mucus plug formation and common genetic backgrounds including TSLP/IL-33 pathway genes seem to underlie these diseases. 153,154 In addition, each disease exhibits a specific pathophysiology such as mast cell and platelet activation in N-ERD, fungal sensitization in ABPA/ABPM, abnormality in coagulation/fibrinolysis pathway in CRSwNP/eosinophilic CRS and autoimmunity in EGPA. The clinical efficacy of anti-IL-5 treatments was also variable among the diseases, high for eosinophilic asthma, ABPA/ABPM and EGPA, whereas low for N-ERD and CRSwNP/eosinophilic CRS (Table 1).…”

Section: Con Clus Ionmentioning

confidence: 99%

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Adult‐onset eosinophilic airway diseases

Asano

Ueki

Tamari

et al. 2020

Allergy

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Allergic diseases in the upper and the lower airways such as allergic rhinitis and atopic asthma are usually accompanied by local eosinophilia and sometimes by peripheral blood eosinophilia. Chronic rhinosinusitis with nasal polyps (CRSwNP) and nonatopic asthma are also characterized by local and systemic eosinophilia; however, there are substantial differences in the age of onset and the presence of atopy. Atopic asthma and allergic rhinitis develop during childhood in most cases and mediated by type 1 hypersensitivity reactions to allergen(s), as are other childhood-onset allergic diseases such as food allergies and eczema. Patients often develop these diseases consecutively as an allergic march (Figure 1), suggesting the presence of common genetic backgrounds and pathophysiology. In contrast to childhood-onset disease, adult-onset asthma frequently presents as a nonatopic and eosinophilic condition, 1-6

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Section: Resultsmentioning

confidence: 99%

Section: Con Clus Ionmentioning

confidence: 99%

Adult‐onset eosinophilic airway diseases

Asano

Ueki

Tamari

et al. 2020

Allergy

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“…Within this context, a key role is played by the innate cytokines known as alarmins, including TSLP, IL-33, and IL-25 (142). So far, the most extensively studied alarmin as suitable target for novel biological therapies of asthma has been TSLP (13,143).…”

Section: Targets Of Emerging Biological Therapies In Clinical Developmentioning

confidence: 99%

“…The latter mainly consist of already licensed monoclonal antibodies targeting specific molecules involved in the pathobiology of type 2 (T2-high) eosinophilic, allergic and non-allergic asthma, including immunoglobulins E (IgE), interleukin-5 (IL-5) and its receptor, as well as interleukin-4 (IL-4) receptor (9)(10)(11). Other experimental biologics target upstream innate cytokines such as thymic stromal lymphopoietin (TSLP) (12,13). Conversely, current pharmacotherapeutic pipelines are very scarce with regard to investigational drugs directed against molecular targets implicated in the pathogenesis of T2-low, mostly neutrophilic severe asthma.…”

Section: Introductionmentioning

confidence: 99%

Molecular Targets for Biological Therapies of Severe Asthma

et al. 2020

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Asthma is a heterogeneous respiratory disease characterized by usually reversible bronchial obstruction, which is clinically expressed by different phenotypes driven by complex pathobiological mechanisms (endotypes). Within this context, during the last years several molecular effectors and signalling pathways have emerged as suitable targets for biological therapies of severe asthma, refractory to standard treatments. Indeed, various therapeutic antibodies currently allow to intercept at different levels the chain of pathogenic events leading to type 2 (T2) airway inflammation. In addition to pro-allergic immunoglobulin E (IgE), that chronologically represents the first molecule against which an anti-asthma monoclonal antibody (omalizumab) was developed, today other targets are successfully exploited by biological treatments of severe asthma. In particular, pro-eosinophilic interleukin 5 (IL-5) can be targeted by mepolizumab or reslizumab, whereas benralizumab is a selective blocker of IL-5 receptor. Moreover, dupilumab behaves as a dual receptor antagonist of pleiotropic interleukins 4 (IL-4) and 13 (IL-13). Besides these drugs that are already available in medical practice, other biologics are under clinical development such as those targeting innate cytokines, also including the alarmin thymic stromal lymphopoietin (TSLP), which plays a key role in the pathogenesis of type 2 asthma. Therefore, ongoing and future biological therapies are significantly changing the global scenario of severe asthma management. These new therapeutic options make it possible to implement phenotype/endotype-specific treatments, that are delineating personalized approaches precisely addressing the individual traits of asthma pathobiology. Such tailored strategies are thus allowing to successfully target the immune-inflammatory responses underlying uncontrolled T2-high asthma.

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“…TSLPaktivierte dendritische Zellen induzieren die Produktion von Th2-Zytokinen (IL-4, IL-5 und IL-13) sowie TNF-α. TSLP wurde in läsionaler Haut von AD-Patienten vermehrt vorgefunden [24]. Es könnte somit ein wichtiger Schlüssel zur Kontrolle von Th2-assoziierten Entzündungen und Störungen der Hautbarriere in der AD sein.…”

Section: Tezepelumab: Anti-tslp Mabunclassified

Biologika-Therapie der atopischen Dermatitis

Bangert

2020

hautnah

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ZusammenfassungDie atopische Dermatitis (AD) ist eine chronisch-entzündliche Hauterkrankung, die mit quälendem Juckreiz, entzündlichen ekzematösen Läsionen, erhöhtem Risiko für sekundäre Hautinfektionen und einer dadurch stark verminderten Lebensqualität einhergeht. Die AD ist durch eine dominante T-Helfer-Typ 2(Th2)-Immunantwort gekennzeichnet, die von T2-Zytokinen, wie Interleukin(IL)-4 und IL-13 dominiert wird, welche eine Entzündungsreaktion sowie Dysfunktion der epidermalen Barriere hervorrufen. Das therapeutische Ziel der AD besteht in der Verbesserung des Juckreizes und der entzündlichen Hautveränderungen. Die Therapieoptionen waren bisher limitiert und bestanden hauptsächlich aus rückfettender Pflege, topischen Kortikosteroiden (TCS) und systemischen Immunsuppressiva, die mit zahlreichen Nebenwirkungen verbunden sind. Neue Erkenntnisse in der Pathophysiologie der AD haben es ermöglicht, moderne Behandlungsoptionen zu entwickeln, die selektiv auf krankheitsverursachende Pfade abzielen und diese blockieren. Dupilumab, ein vollständig humaner monoklonaler Antikörper, der gegen die alpha-Untereinheit des IL-4-Rezeptors gerichtet ist, war das erste Biologikum, das im Jahr 2017 von der FDA und EMA für die Therapie der AD zugelassen wurde. In diesem Artikel stellen wir neue therapeutische Ansätze vor, die entweder kürzlich zugelassen wurden oder derzeit mit viel versprechendem Erfolg in klinischen Studien zur Behandlung von AD eingesetzt werden. Die meisten Behandlungsmöglichkeiten sind derzeit auf Erwachsene und Jugendliche mit schwerer, refraktärer AD beschränkt.

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Anti-TSLP antibodies: Targeting a master regulator of type 2 immune responses

Cited by 67 publications

References 83 publications

Adult‐onset eosinophilic airway diseases

Adult‐onset eosinophilic airway diseases

Molecular Targets for Biological Therapies of Severe Asthma

Biologika-Therapie der atopischen Dermatitis

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