Development of an inhaled anti-TSLP therapy for asthma

O’Byrne, Paul M.; Panettieri, Reynold A.; Taube, Christian; Brindicci, Caterina; Fleming, Margaret; Altman, Pablo

doi:10.1016/j.pupt.2022.102184

Cited by 12 publications

(5 citation statements)

References 118 publications

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“…While these IL-33/ST2-targeting biologics have not yet received FDA approval, some are now in phase 3 clinical trials. The drugs that block the TSLP pathway include tezepelumab, which recently received FDA approval for asthma, and ecleralimab (formerly CSJ117), which is an inhaled drug that is in phase 2 clinical trials (ClinicalTrials.gov Identifier: NCT04882124) 151 . Clinical trials on drugs against IL-25 have not yet been conducted.…”

Section: Ilc-targeting Therapeutic Applications: Current Methodologie...mentioning

confidence: 99%

Versatile roles of innate lymphoid cells at the mucosal barrier: from homeostasis to pathological inflammation

Ryu,

Lim,

Kim

et al. 2023

Exp Mol Med

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Innate lymphoid cells (ILCs) are innate lymphocytes that do not express antigen-specific receptors and largely reside and self-renew in mucosal tissues. ILCs can be categorized into three groups (ILC1–3) based on the transcription factors that direct their functions and the cytokines they produce. Their signature transcription factors and cytokines closely mirror those of their Th1, Th2, and Th17 cell counterparts. Accumulating studies show that ILCs are involved in not only the pathogenesis of mucosal tissue diseases, especially respiratory diseases, and colitis, but also the resolution of such diseases. Here, we discuss recent advances regarding our understanding of the biology of ILCs in mucosal tissue health and disease. In addition, we describe the current research on the immune checkpoints by which other cells regulate ILC activities: for example, checkpoint molecules are potential new targets for therapies that aim to control ILCs in mucosal diseases. In addition, we review approved and clinically- trialed drugs and drugs in clinical trials that can target ILCs and therefore have therapeutic potential in ILC-mediated diseases. Finally, since ILCs also play important roles in mucosal tissue homeostasis, we explore the hitherto sparse research on cell therapy with regulatory ILCs. This review highlights various therapeutic approaches that could be used to treat ILC-mediated mucosal diseases and areas of research that could benefit from further investigation.

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Section: Ilc-targeting Therapeutic Applications: Current Methodologie...mentioning

confidence: 99%

Versatile roles of innate lymphoid cells at the mucosal barrier: from homeostasis to pathological inflammation

Ryu,

Lim,

Kim

et al. 2023

Exp Mol Med

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“…Together, these data suggest that the balance between T2 inflammation and type I interferon/IRF7 responses may stem from the bone marrow, far from the site of peripheral inflammation, as reported in other contexts ( 56 ). They also highlight the potential for new biologic drugs targeting TSLP ( 57 , 58 ) and the downstream effectors IL-13 and IL-17A ( 59 ) to attenuate inflammatory responses to RSV infection in early life.…”

Section: Interferon Response Patterns and The Lung-blood-bone Marrow ...mentioning

confidence: 99%

Emerging role for interferons in respiratory viral infections and childhood asthma

Bosco

2023

Front. Immunol.

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Respiratory syncytial virus (RSV) and Rhinovirus (RV) infections are major triggers of severe lower respiratory illnesses (sLRI) in infants and children and are strongly associated with the subsequent development of asthma. Decades of research has focused on the role of type I interferons in antiviral immunity and ensuing airway diseases, however, recent findings have highlighted several novel aspects of the interferon response that merit further investigation. In this perspective, we discuss emerging roles of type I interferons in the pathogenesis of sLRI in children. We propose that variations in interferon response patterns exist as discrete endotypes, which operate locally in the airways and systemically through a lung-blood-bone marrow axis. We discuss new insights into the role of interferons in immune training, bacterial lysate immunotherapy, and allergen-specific immunotherapy. Interferons play complex and diverse roles in the pathogenesis of sLRI and later asthma, providing new directions for mechanistic studies and drug development.

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“…Especially for patients with a T2-low asthma phenotype, more treatment options must become available. Phase II clinical trials are now running to test ecleralimab, the first inhaled anti-TSLP therapy for treating severe asthma [ 111 ]. Ecleralimab is a neutralizing antibody fragment directed against human TSLP and formulated as a powder for delivery to the lungs through an inhaler device.…”

Section: Future Perspectivesmentioning

confidence: 99%

Developments in the Management of Severe Asthma in Children and Adolescents: Focus on Dupilumab and Tezepelumab

van Dijk,

Rutjes,

Golebski

et al. 2023

Pediatr Drugs

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Severe asthma in children and adolescents exerts a substantial health, financial, and societal burden. Severe asthma is a heterogeneous condition with multiple clinical phenotypes and underlying inflammatory patterns that might be different in individual patients. Various add-on treatments have been developed to treat severe asthma, including monoclonal antibodies (biologics) targeting inflammatory mediators. Biologics that are currently approved to treat children (≥ 6 years of age) or adolescents (≥ 12 years of age) with severe asthma include: anti-immunoglobulin E (omalizumab), anti-interleukin (IL)-5 (mepolizumab), anti-IL5 receptor (benralizumab), anti-IL4/IL13 receptor (dupilumab), and antithymic stromal lymphopoietin (TSLP) (tezepelumab). However, access to these targeted treatments varies across countries and relies on few and crude indicators. There is a need for better treatment stratification to guide which children might benefit from these treatments. In this narrative review we will assess the most recent developments in the treatment of severe pediatric asthma, as well as potential biomarkers to assess treatment efficacy for this patient population.

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Development of an inhaled anti-TSLP therapy for asthma

Cited by 12 publications

References 118 publications

Versatile roles of innate lymphoid cells at the mucosal barrier: from homeostasis to pathological inflammation

Versatile roles of innate lymphoid cells at the mucosal barrier: from homeostasis to pathological inflammation

Emerging role for interferons in respiratory viral infections and childhood asthma

Developments in the Management of Severe Asthma in Children and Adolescents: Focus on Dupilumab and Tezepelumab

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