Treatment with anti‐cytokine monoclonal antibodies can potentiate the target cytokine rather than neutralize its activity

Rudulier, Christopher D.; Larché, Mark; Moldaver, Daniel M.

doi:10.1111/all.12816

Cited by 10 publications

(6 citation statements)

References 31 publications

(42 reference statements)

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“…However, there are some important risks to the use of mAbs including acute anaphylaxis, susceptibility to infections and cancer, serum sickness and the generation of antibodies against the treatment ( Hansel et al, 2010 ). In addition, mAbs targeting cytokines, rather than their receptors, can enhance the secretion or signaling of the target molecule ( Rudulier et al, 2016 ). Appropriate selection and monitoring of specific mAb-therapies should be implemented to minimize side effects during treatment of respiratory diseases.…”

Section: Inflammation In the Lungs: The Good The Bad And The Uglymentioning

confidence: 99%

Novel Immunomodulatory Therapies for Respiratory Pathologies

Tavares

Galvão

Ferrero

2022

Comprehensive Pharmacology

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Section: Inflammation In the Lungs: The Good The Bad And The Uglymentioning

confidence: 99%

Novel Immunomodulatory Therapies for Respiratory Pathologies

Tavares

Galvão

Ferrero

2022

Comprehensive Pharmacology

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“…As it acts directly on the IL5 receptor on eosinophils to cause apoptosis, benralizumab is arguably more effective than mepolizumab and reslizumab, which act indirectly to give incomplete depletion of eosinophils. Using a direct approach also avoids potentiation of the target cytokine through formation of cytokine/anti-cytokine immune complex, which has been reported to occur with anti-cytokine antibodies [ 74 ].…”

Section: Blood Eosinophils As Biomarkers Of Eosinophilia: Clinical Stmentioning

confidence: 99%

Blood Eosinophils as Biomarkers to Drive Treatment Choices in Asthma and COPD

Κostikas

Brindicci

Patalano

2018

CDT

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Background: Asthma and COPD are complex, heterogeneous conditions comprising a wide range of phenotypes, some of which are refractory to currently available treatments. Elucidation of these phenotypes and identification of biomarkers with which to recognize them and guide appropriate treat-ment remain a priority.Objective: This review describes the utility of blood eosinophils as a surrogate biomarker of eosinophilic airway inflammation, a common feature of specific asthma and COPD phenotypes. The role of blood eosinophils in airway disease is described, as is their relevance in reflecting airway eosinophilia. Each disease is discussed separately as the manner in which blood eosinophils might be used as biomarkers differs. Focusing on patients with severe disease (persistent eosinophilic asthma and exacerbating COPD), we evaluate evidence examining eosinophils as biomarkers.Results: In asthma, the rationale for using blood eosinophils to guide treatment is clearly defined, backed by prospective, well-controlled studies. Higher eosinophil counts identify patients with more se-vere disease and poorer outcomes, patients for whom biologic therapies targeting allergic and/or eosino-philic pathways are recommended. In COPD, the evidence is less robust. High blood eosinophil counts are a modest predictor of future exacerbations, and may predict a favourable response to ICS on top of LABA/LAMA, especially in patients with a history of frequent exacerbations.Conclusion: Before extensive application in clinical practice, further evaluation of these findings in pro-spective clinical studies, and standardization of the appropriate thresholds of clinically relevant eosino-philia are needed, together with establishing whether single or multiple measurements are required in dif-ferent clinical settings

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“…Recent findings suggest that, under certain conditions, treatment with anti-cytokine monoclonal antibodies can potentiate the target cytokine rather than neutralise its activity [71]. This is likely due to the formation of cytokine/anti-cytokine complexes, which might explain why targeting cytokines could be clinically inefficient if the employed doses of the monoclonal antibody are low enough to favour the formation of these immune complexes [71].…”

Section: Should Ige Blocking Be a Key Therapeutic Target For Allermentioning

confidence: 99%

“…This is likely due to the formation of cytokine/anti-cytokine complexes, which might explain why targeting cytokines could be clinically inefficient if the employed doses of the monoclonal antibody are low enough to favour the formation of these immune complexes [71]. It should be also borne in mind, in any case, that IgE blockade also indirectly inhibits the production of Th2 cytokines by memory allergen-specific Th2 cells and MC, thus contributing to inhibit acute early responses, reducing inflammation and maintaining homeostasis [72,73,74].…”

Section: Should Ige Blocking Be a Key Therapeutic Target For Allermentioning

confidence: 99%

dIvergEnt: How IgE Axis Contributes to the Continuum of Allergic Asthma and Anti-IgE Therapies

Palomares

Sánchez-Ramón

Dávila

et al. 2017

IJMS

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Asthma is an airway disease characterised by chronic inflammation with intermittent or permanent symptoms including wheezing, shortness of breath, chest tightness, and cough, which vary in terms of their occurrence, frequency, and intensity. The most common associated feature in the airways of patients with asthma is airway inflammation. In recent decades, efforts have been made to characterise the heterogeneous clinical nature of asthma. The interest in improving the definitions of asthma phenotypes and endotypes is growing, although these classifications do not always correlate with prognosis nor are always appropriate therapeutic approaches. Attempts have been made to identify the most relevant molecular and cellular biomarkers underlying the immunopathophysiological mechanisms of the disease. For almost 50 years, immunoglobulin E (IgE) has been identified as a central factor in allergic asthma, due to its allergen-specific nature. Many of the mechanisms of the inflammatory cascade underlying allergic asthma have already been elucidated, and IgE has been shown to play a fundamental role in the triggering, development, and chronicity of the inflammatory responses within the disease. Blocking IgE with monoclonal antibodies such as omalizumab have demonstrated their efficacy, effectiveness, and safety in treating allergic asthma. A better understanding of the multiple contributions of IgE to the inflammatory continuum of asthma could contribute to the development of novel therapeutic strategies for the disease.

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Treatment with anti‐cytokine monoclonal antibodies can potentiate the target cytokine rather than neutralize its activity

Abstract: Allergy 71 (2016) 283-285

Cited by 10 publications

References 31 publications

Novel Immunomodulatory Therapies for Respiratory Pathologies

Novel Immunomodulatory Therapies for Respiratory Pathologies

Blood Eosinophils as Biomarkers to Drive Treatment Choices in Asthma and COPD

dIvergEnt: How IgE Axis Contributes to the Continuum of Allergic Asthma and Anti-IgE Therapies

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