Targeting TSLP in Asthma
Jane R Parnes,1 Nestor A Molfino,1 Gene Colice,2 Ubaldo Martin,2 Jonathan Corren,3 Andrew Menzies-Gow4 1Amgen, Thousand Oaks, CA, USA; 2AstraZeneca, Gaithersburg, MD, USA; 3University of California, Los Angeles, CA, USA; 4Royal Brompton and Harefield Hospitals, London, UKCorrespondence: Jane R Parne...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2022-06-01
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| Series: | Journal of Asthma and Allergy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/targeting-tslp-in-asthma-peer-reviewed-fulltext-article-JAA |
| _version_ | 1811345303999086592 |
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| author | Parnes JR Molfino NA Colice G Martin U Corren J Menzies-Gow A |
| author_facet | Parnes JR Molfino NA Colice G Martin U Corren J Menzies-Gow A |
| author_sort | Parnes JR |
| collection | DOAJ |
| description | Jane R Parnes,1 Nestor A Molfino,1 Gene Colice,2 Ubaldo Martin,2 Jonathan Corren,3 Andrew Menzies-Gow4 1Amgen, Thousand Oaks, CA, USA; 2AstraZeneca, Gaithersburg, MD, USA; 3University of California, Los Angeles, CA, USA; 4Royal Brompton and Harefield Hospitals, London, UKCorrespondence: Jane R Parnes, Amgen, Thousand Oaks, CA, USA, Email jparnes@amgen.comAbstract: Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine implicated in the initiation and persistence of inflammatory pathways in asthma. Released in response to a range of epithelial insults (eg, allergens, viruses, bacteria, pollutants, and smoke), TSLP initiates multiple downstream innate and adaptive immune responses involved in asthma inflammation. Inhibition of TSLP is postulated to represent a novel approach to treating the diverse phenotypes and endotypes of asthma. Tezepelumab, the TSLP inhibitor farthest along in clinical development, is a human monoclonal antibody (IgG2λ) that binds specifically to TSLP, preventing interactions with its heterodimeric receptor. Results of recently published phase 2 and 3 studies, reviewed in this article, provide evidence of the safety and efficacy of tezepelumab that builds on initial findings. Tezepelumab is safe, well tolerated, and provides clinically meaningful improvements in asthma control, including reduced incidence of exacerbations and hospitalizations in patients with severe asthma. Clinical benefits were associated with reductions in levels of a broad spectrum of cytokines (eg, interleukin [IL]-5, IL-13) and baseline biomarkers (eg, blood eosinophils, immunoglobulin [Ig]E, fractional exhaled nitric oxide [FeNO]) and were observed across a range of severe asthma phenotypes (ie, eosinophilic and non-eosinophilic). These data strengthen the notion that anti-TSLP elicits broad inhibitory effects on pathways that are key to asthma inflammation rather than on narrower inhibition of individual downstream factors. This review presents the rationale for targeting TSLP to treat asthma, as well as the clinical effects of TSLP blockade on asthma outcomes, biomarkers of disease activity, airway inflammation, lung physiology, and patient symptoms.Keywords: thymic stromal lymphopoietin, TSLP, asthma, exacerbation rates, anti-TSLP |
| first_indexed | 2024-04-13T20:01:08Z |
| format | Article |
| id | doaj.art-530f24393c234a85b70016ba4f2b9516 |
| institution | Directory Open Access Journal |
| issn | 1178-6965 |
| language | English |
| last_indexed | 2024-04-13T20:01:08Z |
| publishDate | 2022-06-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Asthma and Allergy |
| spelling | doaj.art-530f24393c234a85b70016ba4f2b95162022-12-22T02:32:12ZengDove Medical PressJournal of Asthma and Allergy1178-69652022-06-01Volume 1574976575721Targeting TSLP in AsthmaParnes JRMolfino NAColice GMartin UCorren JMenzies-Gow AJane R Parnes,1 Nestor A Molfino,1 Gene Colice,2 Ubaldo Martin,2 Jonathan Corren,3 Andrew Menzies-Gow4 1Amgen, Thousand Oaks, CA, USA; 2AstraZeneca, Gaithersburg, MD, USA; 3University of California, Los Angeles, CA, USA; 4Royal Brompton and Harefield Hospitals, London, UKCorrespondence: Jane R Parnes, Amgen, Thousand Oaks, CA, USA, Email jparnes@amgen.comAbstract: Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine implicated in the initiation and persistence of inflammatory pathways in asthma. Released in response to a range of epithelial insults (eg, allergens, viruses, bacteria, pollutants, and smoke), TSLP initiates multiple downstream innate and adaptive immune responses involved in asthma inflammation. Inhibition of TSLP is postulated to represent a novel approach to treating the diverse phenotypes and endotypes of asthma. Tezepelumab, the TSLP inhibitor farthest along in clinical development, is a human monoclonal antibody (IgG2λ) that binds specifically to TSLP, preventing interactions with its heterodimeric receptor. Results of recently published phase 2 and 3 studies, reviewed in this article, provide evidence of the safety and efficacy of tezepelumab that builds on initial findings. Tezepelumab is safe, well tolerated, and provides clinically meaningful improvements in asthma control, including reduced incidence of exacerbations and hospitalizations in patients with severe asthma. Clinical benefits were associated with reductions in levels of a broad spectrum of cytokines (eg, interleukin [IL]-5, IL-13) and baseline biomarkers (eg, blood eosinophils, immunoglobulin [Ig]E, fractional exhaled nitric oxide [FeNO]) and were observed across a range of severe asthma phenotypes (ie, eosinophilic and non-eosinophilic). These data strengthen the notion that anti-TSLP elicits broad inhibitory effects on pathways that are key to asthma inflammation rather than on narrower inhibition of individual downstream factors. This review presents the rationale for targeting TSLP to treat asthma, as well as the clinical effects of TSLP blockade on asthma outcomes, biomarkers of disease activity, airway inflammation, lung physiology, and patient symptoms.Keywords: thymic stromal lymphopoietin, TSLP, asthma, exacerbation rates, anti-TSLPhttps://www.dovepress.com/targeting-tslp-in-asthma-peer-reviewed-fulltext-article-JAAthymic stromal lymphopoietintslpasthmaexacerbation ratesanti-tslp |
| spellingShingle | Parnes JR Molfino NA Colice G Martin U Corren J Menzies-Gow A Targeting TSLP in Asthma Journal of Asthma and Allergy thymic stromal lymphopoietin tslp asthma exacerbation rates anti-tslp |
| title | Targeting TSLP in Asthma |
| title_full | Targeting TSLP in Asthma |
| title_fullStr | Targeting TSLP in Asthma |
| title_full_unstemmed | Targeting TSLP in Asthma |
| title_short | Targeting TSLP in Asthma |
| title_sort | targeting tslp in asthma |
| topic | thymic stromal lymphopoietin tslp asthma exacerbation rates anti-tslp |
| url | https://www.dovepress.com/targeting-tslp-in-asthma-peer-reviewed-fulltext-article-JAA |
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