Novel monoclonal treatments in severe asthma

Meteran, Howraman; Meteran, Hanieh; Porsbjerg, Celeste; Backer, Vibeke

doi:10.1080/02770903.2017.1296157

Cited by 9 publications

(8 citation statements)

References 63 publications

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“…If we look at the human clinical studies for emerging monoclonal antibodies in treating asthma for the past 20 years, studies targeting IgE, IL-2, IL4R-alpha, IL-5, and IL-13 showed some efficacy, however those targeting TNF-alpha, TSLP and IL-9 did not show convincing effectiveness [38] and no asthma clinical trials targeting IL-6 have been conducted to the best of our knowledge. It is likely that TNF-alpha and IL-6 may not be the culprits of allergic airway inflammation and may be merely one of the biomarkers participating the inflammatory cascade.…”

Section: Discussionmentioning

confidence: 99%

Oral edible plant vaccine containing hypoallergen of American cockroach major allergen Per a 2 prevents roach-allergic asthma in a murine model

Lee

Chiang

et al. 2018

PLoS ONE

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BackgroundAmerican cockroaches (Periplaneta americana) are an important indoor allergen source and a major risk factor for exacerbations and poor control of asthma. We previously reported that allergen components from American cockroaches exhibit varying levels of pathogenicity. Sensitization to major American cockroach allergen, Per a 2, correlated with more severe clinical phenotypes among patients with allergic airway diseases.Materials and methodsIn this study, we examined whether oral plant vaccine-encoding full-length Per a 2 clone-996 or its hypoallergenic clone-372 could exert a prophylactic role in Per a 2-sensitized mice. The cDNAs coding Per a 2–996 and Per a 2–372 were inserted into TuMV vector and expressed in Chinese cabbage. Adult female BALB/c mice were fed with the cabbage extracts for 21 days and subsequently underwent two-step sensitization with recombinant Per a 2.ResultsPer a 2-specific IgE measured by in-house ELISA in the sera of Per a 2-372-treated groups were significantly lower than in the control groups after allergen challenge but not the Per a 2-996-treated group. Moreover, Per a 2–372 vaccine markedly decreased airway hyper-responsiveness and infiltration of inflammatory cells into the lungs, as well as reduced mRNA expression of IL-4 and IL-13 in comparison with the control mice.ConclusionOur data suggest that oral administration of edible plant vaccine encoding Per a 2 hypo-allergen may be used as a prophylactic strategy against the development of cockroach allergy.

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Section: Discussionmentioning

confidence: 99%

Oral edible plant vaccine containing hypoallergen of American cockroach major allergen Per a 2 prevents roach-allergic asthma in a murine model

Lee

Chiang

et al. 2018

PLoS ONE

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“…9 Key in the IL-4/IL-13 axis is the IL-4Rα signaling which has been identified as a potential target for asthma therapies. [12][13][14] Deficiency of IL-4Rα in allergen-sensitized mice shows reduced allergen-induced symptoms such as AHR, eosinophilia, and mucus hyperplasia in vivo. [15][16][17] We and others have also illustrated various cell-specific roles of IL-4Rα signaling during the development of allergic disease pathology.…”

Section: Introductionmentioning

confidence: 99%

“…Key in the IL‐4/IL‐13 axis is the IL‐4Rα signaling which has been identified as a potential target for asthma therapies . Deficiency of IL‐4Rα in allergen‐sensitized mice shows reduced allergen‐induced symptoms such as AHR, eosinophilia, and mucus hyperplasia in vivo .…”

Section: Introductionmentioning

confidence: 99%

Therapeutic and prophylactic deletion of IL‐4Ra‐signaling ameliorates established ovalbumin induced allergic asthma

Khumalo

Kirstein

Scibiorek

et al. 2020

Allergy

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Background: Allergic asthma is a chronic inflammatory airway disease driven predominantly by a T H 2 immune response to environmental allergens. IL-4Rα-signaling is essential for driving T H 2-type immunity to allergens. Anti-T H 2 therapies have the potential to effectively reduce airway obstruction and inflammation in allergic asthma. Objective:We investigated potential therapeutic effects of selective inhibition of this pathway in mice with established allergic airway disease. We further investigated whether IL-4Rα disruption in systemically sensitized mice can prevent the onset of the disease. Methods: We used Rosa creERT2 IL-4Rα −/lox mice, a tamoxifen (TAM)-inducible IL-4Rα knockdown model to investigate the role of IL-4/IL-13 signaling prior to the onset of the disease and during the effector phase in the ovalbumin-induced allergic airway disease. Results: Inducible deletion of IL-4Rα demonstrated therapeutic effects, on established allergic airway disease, and prevented the development of ovalbumin-induced airway hyperreactivity, eosinophilia, and goblet cell metaplasia in allergen-sensitized mice. Interestingly, IL-4Rα knockdown after allergic sensitization did not induce T H 17, a neutrophilic inflammatory response as observed in global IL-4Rα-deficient mice after intranasal allergen challenge.Conclusion: Abrogation of IL-4Rα signaling after allergic sensitization would have significant therapeutic benefit for T H 2-type allergic asthma. K E Y W O R D S IL-4Rα, prophylactic, tamoxifen, T H 2 type, therapeuticThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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“…In the context of severe asthma, it is certainly promising to see the recent development and subsequent licensing of several novel treatments [3]. Indeed, within the past year, a number of biologic agents (e.g.…”

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confidence: 99%

“…Indeed, within the past year, a number of biologic agents (e.g. Mepolizumab and Reslizumab) have become available, targeting a Type-2 inflammatory pattern [3][4][5]. These therapies certainly considerably advance the available treatment options in severe asthma and indeed for many individuals will be transformational.…”

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confidence: 99%