In vitro and in vivo characterisation of anti-murine IL-13 antibodies recognising distinct functional epitopes

Berry, Loren; Adams, Ralph; Airey, Michael; Bracher, Marguerite; Bourne, Tim; Carrington, Bruce; Cross, A.S.; Davies, G C; Finney, Helene; Foulkes, Roly; Gozzard, Neil; Griffin, Robert; Hailu, Hanna; Lamour, Sabrina; Lawson, Alastair D. G.; Lightwood, Daniel; McKnight, Andrew J.; O’Dowd, Victoria; Oxbrow, Amanda K. F.; Popplewell, Andy; Shaw, Stevan; Stephens, Paul E.; Sweeney, Bernadette; Tomlinson, Kate L.; Uhe, C.; Palframan, Roger

doi:10.1016/j.intimp.2008.11.001

Cited by 11 publications

(6 citation statements)

References 29 publications

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“…Murinised anti-mouse IL-13 mAb (CA154_582, mAb A) was generated by UCB and in vitro activity was characterised as reported previously [39]. CA154_582 prevents the interaction between IL-13 and IL-13Rα1 and hence the subsequent association with IL-4Rα (K D 11pM).…”

Section: Methodsmentioning

confidence: 99%

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Neutralisation of Interleukin-13 in Mice Prevents Airway Pathology Caused by Chronic Exposure to House Dust Mite

et al. 2010

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BackgroundRepeated exposure to inhaled allergen can cause airway inflammation, remodeling and dysfunction that manifests as the symptoms of allergic asthma. We have investigated the role of the cytokine interleukin-13 (IL-13) in the generation and persistence of airway cellular inflammation, bronchial remodeling and deterioration in airway function in a model of allergic asthma caused by chronic exposure to the aeroallergen House Dust Mite (HDM).Methodology/Principal FindingsMice were exposed to HDM via the intranasal route for 4 consecutive days per week for up to 8 consecutive weeks. Mice were treated either prophylactically or therapeutically with a potent neutralising anti-IL-13 monoclonal antibody (mAb) administered subcutaneously (s.c.). Airway cellular inflammation was assessed by flow cytometry, peribronchial collagen deposition by histocytochemistry and airway hyperreactivity (AHR) by invasive measurement of lung resistance (RL) and dynamic compliance (Cdyn). Both prophylactic and therapeutic treatment with an anti-IL-13 mAb significantly inhibited (P<0.05) the generation and maintenance of chronic HDM-induced airway cellular inflammation, peribronchial collagen deposition, epithelial goblet cell upregulation. AHR to inhaled methacholine was reversed by prophylactic but not therapeutic treatment with anti-IL-13 mAb. Both prophylactic and therapeutic treatment with anti-IL-13 mAb significantly reversed (P<0.05) the increase in baseline RL and the decrease in baseline Cdyn caused by chronic exposure to inhaled HDM.Conclusions/SignificanceThese data demonstrate that in a model of allergic lung disease driven by chronic exposure to a clinically relevant aeroallergen, IL-13 plays a significant role in the generation and persistence of airway inflammation, remodeling and dysfunction.

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Section: Methodsmentioning

confidence: 99%

“…Lung tissue IL-13 mRNA levels were determined in medial lung lobes relative to 18S expression as previously described in detail [39]. IL-13 mRNA expression was normalised to that of lungs from animals exposed to saline.…”

Section: Methodsmentioning

confidence: 99%

Neutralisation of Interleukin-13 in Mice Prevents Airway Pathology Caused by Chronic Exposure to House Dust Mite

et al. 2010

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“… 21 One study evaluated the use of IL-13 monoclonal antibodies in murine models. 22 Two antibodies were generated, with slightly distinct mechanisms of action in terms of IL-13 inhibition. One antibody was shown to bind to mouse IL-13 and prevent its binding to mIL-13Rα1; the other antibody similarly targeted IL-13 but instead prevented the assembly of IL-4Rα with the IL-13/IL-13Rα1 complex.…”

Section: Preclinical Pharmacologymentioning

confidence: 99%

Managing Atopic Dermatitis with Lebrikizumab – The Evidence to Date

Labib¹,

Ju²,

Yosipovitch³

2022

CCID

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Atopic dermatitis is a prevalent, inflammatory skin disease that presents with an eczematous, itchy rash. As of late, there have been many emerging monoclonal antibody inhibitor and small molecule therapies that have changed the course of eczema treatment. One of the treatments in the pipeline for atopic dermatitis is interleukin 13 monoclonal antibody inhibitor, lebrikizumab. As interleukin 13 has been identified as a pro-inflammatory cytokine in the immunological cascade of eczema, it is thought that lebrikizumab can be a great treatment choice for patients with atopic dermatitis. Lebrikizumab is currently being investigated in several studies. Thus far, lebrikizumab for the treatment of eczema has been found to be efficacious; in particular, a rapid response of pruritus improvement has been demonstrated in as early as 2 days. Additionally, it is well tolerated and has an acceptable safety profile, with reports suggesting that are decreased risks of infection when compared to dupilumab. In this review, we aim to summarize the current understanding of lebrikizumab in terms of the mechanism of action, preclinical pharmacology, pharmacokinetics and metabolism, efficacy and safety, and drug indications.

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“…More recently, methods to identify antibodies in a more efficient manner have been employed. These include culture and expansion of antibody-producing B cells from immunized rodents using CD40/CD40L (Wen et al 1987;Weber et al 2003) as well as flow cytometry-based sorting of antibody-producing cells (APCs) using fluorescently labeled antigen followed by reverse transcription polymerase chain reaction (RT-PCR) from cells (Berry et al 2009;Kurosawa et al 2012).…”

Section: Approaches To Antibody Isolationmentioning

confidence: 99%

Selecting an Optimal Antibody for Antibody- Drug Conjugate Therapy

Ritchie

Bloom

Carven

et al. 2015

Antibody-Drug Conjugates

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Selection of appropriate targets is likely the most important consideration for the success of an antibody-drug conjugate (ADC) development program. Target selection for ADCs can be classified into two principal approaches: target-first and antibody-first approach or agnostic approach (Fig. 3.1). In the target-first approach, a target is chosen based on a set of factors, including expression pattern, abundance and internalization properties, and an antibody-generation campaign is focused on isolation of antibodies against this target. In the agnostic approach, antibodies capable of binding to and internalizing in tumor cells are isolated, followed by retrospective identification of their targets. While the target-first approach may have the advantage of a higher degree confidence in the suitability and novelty of the target based on prior knowledge of target properties, it requires significant work before internalizing antibodies become available. By contrast, the agnostic approach leads quickly to reagents suitable for testing hypotheses directly, although this strategy tends to favor highly expressed surface antigens, which are likely to have been described previously.

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In vitro and in vivo characterisation of anti-murine IL-13 antibodies recognising distinct functional epitopes

Cited by 11 publications

References 29 publications

Neutralisation of Interleukin-13 in Mice Prevents Airway Pathology Caused by Chronic Exposure to House Dust Mite

Neutralisation of Interleukin-13 in Mice Prevents Airway Pathology Caused by Chronic Exposure to House Dust Mite

Managing Atopic Dermatitis with Lebrikizumab – The Evidence to Date

Selecting an Optimal Antibody for Antibody- Drug Conjugate Therapy

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