REGN1908/1909 prevented cat allergen–induced early asthmatic responses in an environmental exposure unit

Blay, Frederic J. de; Gherasim, Alina; Domis, Nathalie; Meier, Pretty; Shawki, Furat; Wang, Claire Q.F.; Orengo, Jamie M.; DeVeaux, Michelle; Ramesh, Divya; Jalbert, Jessica J.; Kamal, Mohamed; Abdallah, Hisham; Dingman, Robert; Perlee, Lorah; Weinreich, David M.; Herman, Gary; Yancopouloš, George D.; O’Brien, Meagan P.

doi:10.1016/j.jaci.2022.06.025

Cited by 20 publications

(12 citation statements)

References 49 publications

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“…The prolonged availability of a protective nanobody in the circulation will be of great importance to defend against repeated allergen contact during the pollen season. In this context, pharmacokinetic/pharmacodynamic studies have already demonstrated that antibody quantities of 10 mg/l suffice to block Bet v 1 or Fel d 1-induced mast cell degranulation in passive cutaneous anaphylaxis mouse models and offer sustained inhibition of nasal allergic symptoms provoked by birch pollen ( 20 , 22 – 24 ).…”

Section: Discussionmentioning

confidence: 99%

“…This inconsistent efficacy and the knowledge that successful AIT is dependent on the boost of allergen-specific IgG antibodies that compete with patients´ IgE antibodies for allergen binding, led to the first allergen-specific antibody-based approaches for allergy treatment ( 19 , 20 ). Efficient reduction of allergic symptoms in cat and birch pollen-sensitized patients using preselected potent monoclonal IgG antibodies as biologics has already been demonstrated as a rapid and reliable treatment option for allergy ( 21 – 24 ).…”

Section: Introductionmentioning

confidence: 99%

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Trimeric Bet v 1-specific nanobodies cause strong suppression of IgE binding

Bauernfeind,

Zettl,

Ivanova

et al. 2024

Front. Immunol.

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BackgroundAround 20% of the population in Northern and Central Europe is affected by birch pollen allergy, with the major birch pollen allergen Bet v 1 as the main elicitor of allergic reactions. Together with its cross-reactive allergens from related trees and foods, Bet v 1 causes an impaired quality of life. Hence, new treatment strategies were elaborated, demonstrating the effectiveness of blocking IgG antibodies on Bet v 1-induced IgE-mediated reactions. A recent study provided evidence for the first time that Bet v 1-specific nanobodies reduce patients´ IgE binding to Bet v 1. In order to increase the potential to outcompete IgE recognition of Bet v 1 and to foster cross-reactivity and cross-protection, we developed Bet v 1-specific nanobody trimers and evaluated their capacity to suppress polyclonal IgE binding to corresponding allergens and allergen-induced basophil degranulation.MethodsNanobody trimers were engineered by adding isoleucine zippers, thus enabling trimeric formation. Trimers were analyzed for their cross-reactivity, binding kinetics to Bet v 1, and related allergens, and patients’ IgE inhibition potential. Finally, their efficacy to prevent basophil degranulation was investigated.ResultsTrimers showed enhanced recognition of cross-reactive allergens and increased efficiency to reduce IgE-allergen binding compared to nanobody monomers. Furthermore, trimers displayed slow dissociation rates from allergens and suppressed allergen-induced mediator release.ConclusionWe generated high-affine nanobody trimers that target Bet v 1 and related allergens. Trimers blocked IgE-allergen interaction by competing with IgE for allergen binding. They inhibited IgE-mediated release of biological mediators, demonstrating a promising potential to prevent allergic reactions caused by Bet v 1 and relatives.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Trimeric Bet v 1-specific nanobodies cause strong suppression of IgE binding

Bauernfeind,

Zettl,

Ivanova

et al. 2024

Front. Immunol.

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“…In the future, more investigations should evaluate the hypersensitive adverse reactions of biological therapies on allergic patients, especially AR. For novel monoclonal antibodies targeting allergic proteins, such as REGN1908-1909 which targets Fel d 1, the dominant allergen in cat dander triggering AR and asthma symptoms [43], and REGN5713/14/15 which targets Bet v 1, the most abundant and immunodominant allergen in birch pollen triggering birch-related AR 12 , the overall safety was acceptable based on the analysis of the included studies. However, the number of trials and patients included were insufficient, and there was no past research indicating tolerability information in other diseases for reference.…”

Section: Discussionmentioning

confidence: 99%

Adverse Events for Monoclonal Antibodies in Patients with Allergic Rhinitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Lin

Wang

Zhu

et al. 2023

JCM

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(1) Background: Allergic rhinitis (AR) is a common disease in otolaryngology and novel biological therapies are required for clinical needs. To assess the tolerability of monoclonal antibodies, justifying their clinical applications, we presented a comprehensive safety profile of biologics in AR; (2) Methods: A systematic literature search was conducted following PRISMA guidelines for randomized clinical trials comparing monoclonal antibodies and placebo in AR. PubMed, Web of Science, Medline, and Cochrane were searched up until 9 January 2023. Among 3590 records in total, 12 studies with more than 2600 patients were included. Quality was assessed for all studies using Cochrane risk-of-bias tool for randomized trials, and subgrouped meta-analysis was performed; (3) Results: We accomplished an up-to-date literature overview and analysis on adverse events of monoclonal antibodies in AR. Total, common, severe, discontinuation-causing, and serious adverse events failed to reach statistical significance. Country was an essential factor for heterogeneity, and urticaria was the adverse event at highest risk (RR 2.81, 95% CI 0.79–9.95); (4) Conclusions: Monoclonal antibodies are considered well tolerated and relatively safe in patients with AR. The regions of patients and hypersensitive adverse reactions such as urticaria require a special caution in biological treatments in AR.

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“…Biologics may be a future approach, but their costeffectiveness is unknown. [4][5][6] An innovation to better manage cat-allergic patients utilised anti-Fel d 1 IgY antibodies to safely and effectively neutralise Fel d 1 after its production by the cat. The efficacy of a feline diet with an egg-product ingredient containing anti-Fel d 1 IgY antibodies was demonstrated in vitro, ex vivo and in vivo, and a pilot exposure study involving cat-allergic human participants suggested its efficacy.…”

Section: Introductionmentioning

confidence: 99%

“…There is a need for innovative approaches to better manage cat allergy. Biologics may be a future approach, but their cost‐effectiveness is unknown 4–6 …”

Section: Introductionmentioning

confidence: 99%

Proof‐of‐concept study of anti‐Fel d 1 IgY antibodies in cat food using the MASK‐air^® app

Bousquet,

Gherasim,

de Blay

et al. 2024

Clinical & Translational All

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BackgroundAn innovation to better manage cat‐allergic patients utilises anti‐Fel d 1 IgY antibodies to neutralise Fel d 1 after its production by the cat. However, there is no published study showing its clinical efficacy in humans in a home setting. A longitudinal, open‐label, proof‐of‐concept study was carried out to approach clinical efficacy of the cat food in cat‐allergic patients.MethodsAfter a baseline evaluation, the cats ate only the cat food for the following 4 months. Daily evaluation of efficacy was performed for 2 weeks at baseline and after 1, 2 and 3 months of intervention for periods of 2 weeks. The MASK‐air app was used daily to assess symptoms, work productivity and medications.ResultsOf the 49 patients screened, 42 were followed up and 33 (78.5%) reported MASK‐air data at all 3 evaluation periods. The primary end point (visual analogue scale [VAS] for global allergy symptoms) was significantly improved (p < 0.0001). All symptoms (VAS nose, eye, and asthma), VAS work and the combined symptom‐medication score significantly improved after 1 month. The percentage of uncontrolled days (VAS>20/100) decreased from 64% at baseline to 35% at 1 month (p < 0.0001) and 14% at 3 months. A sensitivity analysis in patients with uncontrolled disease at baseline found similar results.DiscussionA cat diet containing anti‐Fel d 1 antibodies was able to (i) show decreased allergic symptoms and related outcomes, (ii) inform the design and feasibility of future studies with a control arm and (iii) estimate the sample size of the study.Study registration number: clinicaltrials.gov: NCT05656482.

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REGN1908/1909 prevented cat allergen–induced early asthmatic responses in an environmental exposure unit

Cited by 20 publications

References 49 publications

Trimeric Bet v 1-specific nanobodies cause strong suppression of IgE binding

Trimeric Bet v 1-specific nanobodies cause strong suppression of IgE binding

Adverse Events for Monoclonal Antibodies in Patients with Allergic Rhinitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Proof‐of‐concept study of anti‐Fel d 1 IgY antibodies in cat food using the MASK‐air^® app

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REGN1908/1909 prevented cat allergen–induced early asthmatic responses in an environmental exposure unit

Cited by 20 publications

References 49 publications

Trimeric Bet v 1-specific nanobodies cause strong suppression of IgE binding

Trimeric Bet v 1-specific nanobodies cause strong suppression of IgE binding

Adverse Events for Monoclonal Antibodies in Patients with Allergic Rhinitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Proof‐of‐concept study of anti‐Fel d 1 IgY antibodies in cat food using the MASK‐air® app

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Proof‐of‐concept study of anti‐Fel d 1 IgY antibodies in cat food using the MASK‐air^® app