An overview of the preclinical discovery and development of tezepelumab for the treatment of asthma

Matera, Maria Gabriella; Ora, Josuel; Rogliani, Paola; Cazzola, Mario

doi:10.1080/17460441.2023.2230885

Cited by 3 publications

(1 citation statement)

References 62 publications

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“…By impending the binding of this relevant alarmin in the pathogenesis of asthma with its receptor, tezepelumab inhibits multiple downstream inflammatory pathways and reduces biomarkers and cytokines associated with inflammation including blood eosinophils, airway submucosal eosinophils, FeNO, IgE, IL-5 and IL-13 [ 16 ]. This type of biologic may have advantages by blocking such an upstream mediator with a potentially broader therapeutic impact compared with inhibiting downstream cytokines and/or their receptors [ 127 ].…”

Section: Overview Of the Pharmacological Anti-tslp Strategiesmentioning

confidence: 99%

Thymic Stromal Lymphopoietin (TSLP), Its Isoforms and the Interplay with the Epithelium in Allergy and Asthma

Smolińska

Antolín‐Amérigo

Popescu

et al. 2023

IJMS

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Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine that has emerged as a critical player in the development and progression of allergy and asthma. It is primarily produced by epithelial cells and functions as a potent immune system activator. TSLP acts through interaction with its receptor complex, composed of the TSLP receptor (TSLPR) and interleukin-7 receptor alpha chain (IL-7Rα), activating downstream complex signalling pathways. The TSLP major isoform, known as long-form TSLP (lfTSLP), is upregulated in the airway epithelium of patients with allergic diseases. More research is warranted to explore the precise mechanisms by which short-form TSLP (sfTSLP) regulates immune responses. Understanding the dynamic interplay between TSLP and the dysfunctional epithelium provides insights into the mechanisms underlying allergy and asthma pathogenesis. Targeting TSLP represents an important therapeutic strategy, as it may upstream disrupt the inflammatory cascade and alleviate symptoms associated with allergic inflammation.

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Section: Overview Of the Pharmacological Anti-tslp Strategiesmentioning

confidence: 99%

Thymic Stromal Lymphopoietin (TSLP), Its Isoforms and the Interplay with the Epithelium in Allergy and Asthma

Smolińska

Antolín‐Amérigo

Popescu

et al. 2023

IJMS

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The pharmacological management of asthma in adults: 2023 update

Matera,

Rinaldi,

Annibale

et al. 2024

Expert Opinion on Pharmacotherapy

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New Drug for Management of Severe Uncontrolled Asthma: Tezepelumab

Sharma,

George,

Kumar

et al. 2024

CIS

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Tezepelumab is a first-in-class human IgG2λ monoclonal antibody used to treat severe, uncontrolled asthma. Tezepelumab acts by hindering the action of thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine that triggers an immunological response by binding to TSLP and thereby preventing its binding with the TSLP receptor complex. TSLP has a critical role in Th2 immunity and plays an important role in the pathogenesis of asthma because it stimulates the production of Th2-associated inflammatory mediators, such as interleukin-4, interleukin-5, interleukin-9, and interleukin-13. It is the first biologic with no phenotypic or biomarker restrictions that has been approved for use in severe asthma. Tezepelumab is indicated in severe, uncontrolled asthma patients due to its safety, tolerability, and efficacy. Adults with severe, uncontrolled asthma experienced considerably lower annualised asthma exacerbation rates (AAERs) when administered with tezepelumab compared to a placebo. These preliminary results indicated that the TSLP-induced release of T2 inflammatory mediators may be reduced, and the sustained inhibition was maintained over a 52-week treatment period. In this review, we have summarised various phase III clinical trials and the mechanism of action of tezepelumab in severe, uncontrolled asthma.

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An overview of the preclinical discovery and development of tezepelumab for the treatment of asthma

Cited by 3 publications

References 62 publications

Thymic Stromal Lymphopoietin (TSLP), Its Isoforms and the Interplay with the Epithelium in Allergy and Asthma

Thymic Stromal Lymphopoietin (TSLP), Its Isoforms and the Interplay with the Epithelium in Allergy and Asthma

The pharmacological management of asthma in adults: 2023 update

New Drug for Management of Severe Uncontrolled Asthma: Tezepelumab

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