Development and validation of a cell based assay for the detection of neutralizing antibodies against recombinant insulins

Chatterjee, Sanjukta; Vashishta, Laxmikant; Waichale, Vinit S; Nayak, Vivek G; Melarkode, Ramakrishnan; Donnelly, Charles; Vallano, Patrick T.; Chirmule, Narendra; Sengupta, Nilanjan

doi:10.1016/j.jim.2017.09.004

Cited by 7 publications

(2 citation statements)

References 19 publications

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“…In addition to the choice of screening and confirmatory assays, multiple options for detection of neutralizing antibodies (NAbs) in ADA positive samples also exist [43,44]. Depending on the biologic's mechanism of action (MoA), the selected assay may be cell-based or non-cell-based (Table 1).…”

Section: Drug Tolerance Limitmentioning

confidence: 99%

Comparative Immunogenicity Assessment of Biosimilars

et al. 2018

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The first anticancer biosimilars have entered clinical use, with many others under clinical development. Like all biologics, biosimilars may elicit unwanted immune responses that can significantly impact clinical efficacy and safety. Head-to-head immunogenicity assessment of biosimilars and their reference biologics should, therefore, be a critical component of a biosimilar's clinical development program. Various bioanalytical platforms may be used to detect and characterize immune responses, each having relative strengths and weaknesses. To fully recognize the clinical relevance of such data, regulators must be able to interpret immunogenicity results in an assay-specific context as well as in perspective of clinical pharmacology, efficacy and safety. Herein, we discuss current challenges imposed by global regulatory requirements for immunogenicity assessment of biosimilars.

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Section: Drug Tolerance Limitmentioning

confidence: 99%

Comparative Immunogenicity Assessment of Biosimilars

et al. 2018

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“…This discrepancy may be explained by the type of ADA assay used as studies focussing on NAb rather than on total ADA levels, are more likely to find a correlation with clinical loss of response [9] , [10] . Traditionally, NAb levels are measured with cell-based assays, which quantify the biological activity of a living cell exposed to sample material [11] , [12] . These assays are laborious to perform and may lack specificity due to cross reactivity, e.g.…”

Section: Introductionmentioning

confidence: 99%

Quantification of neutralizing anti-drug antibodies and their neutralizing capacity using competitive displacement and tandem mass spectrometry: Infliximab as proof of principle

Amrani

Göbel

Egas

et al. 2019

Journal of Translational Autoimmunity

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Background The development of anti-drug antibodies (ADA) in patients treated with therapeutic proteins can result in treatment failure. The clinically most relevant fraction of these antibodies are the neutralizing anti-drug antibodies (NAb) that block the pharmacological function of the drug. Consequently, the detection of NAb in plasma is a better predictor of loss of therapeutic response than increased levels of total anti-drug antibodies (ADA) test. Traditional assays to detect ADA and NAb have limited specificity, sensitivity and linear dynamic range. Method Here, we demonstrate for the first time the potential of a LC-MS/MS method to measure the concentration of NAb against therapeutic proteins in plasma as exemplified with infliximab (IFX). We designed a competitive screening assay in which the presence of NAb in patients plasma prevents the binding of stable isotopically labeled (SIL) mAb infliximab to TNF-α ligand fixed on a 96-well plate. Results After washing, eluting and digesting, the signal intensity of SIL IFX-derived signature peptides was inversely and strongly correlated with NAb concentration in the sample: R 2 = 0.999. Evaluation data showed that the assay has a high specificity (100%) and a high sensitivity (94%) to predict NAb presence. Cross-validation against total ADA measured by a reference laboratory using radio immunoassay assay (RIA) for ADA provided a good correlation (r 2 = 0.79). Conclusion We developed for the first time a robust and fast screening method on the basis of LC-MS/MS to determine the presence of NAb and its neutralizing capacity in plasma. The analyses of NAb can be combined with therapeutic mAb quantification. Furthermore, the quantification of the neutralizing capacity expressed as mAb mass equivalents opens the door to new personalized dosing strategies in patients with NAb.

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Amyloidogenicity of peptides targeting diabetes and obesity

Lima

Icart

2022

Colloids and Surfaces B: Biointerfaces

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Development and validation of a cell based assay for the detection of neutralizing antibodies against recombinant insulins

Cited by 7 publications

References 19 publications

Comparative Immunogenicity Assessment of Biosimilars

Comparative Immunogenicity Assessment of Biosimilars

Quantification of neutralizing anti-drug antibodies and their neutralizing capacity using competitive displacement and tandem mass spectrometry: Infliximab as proof of principle

Amyloidogenicity of peptides targeting diabetes and obesity

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