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Sensitivity and drug tolerance of antidrug antibody assays in relation to positive control characteristics.

Authors
  • Egging, David1
  • Verhagen, Jos1
  • Laat-Arts, Karin de1
  • Wit, Benny de1
  • Boekel, Tinie van1
  • Buurman, Marijn2
  • Eigenhuijsen, Jochem1
  • Lubbers-Geuijen, Karin1
  • Mulder, Roel3
  • 1 Preclinical Department, Synthon Biopharmaceuticals B.V., Microweg 22, Nijmegen, The Netherlands. , (Netherlands)
  • 2 Analytical Development & Quality Control Department, Synthon Biopharmaceuticals B.V., Microweg 22, Nijmegen, The Netherlands. , (Netherlands)
  • 3 Clinical Development Department, Synthon Biopharmaceuticals B.V., Microweg 22, Nijmegen, The Netherlands. , (Netherlands)
Type
Published Article
Journal
Bioanalysis
Publisher
"Future Science, LTD"
Publication Date
Aug 01, 2018
Volume
10
Issue
16
Pages
1289–1306
Identifiers
DOI: 10.4155/bio-2018-0091
PMID: 30130133
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Detection and characterization of antidrug antibodies (ADA) play a key role in understanding the relation of ADA with safety and efficacy. Positive controls (PCs) are used to estimate the sensitivity and assay sensitivity in the presence of drug (drug tolerance) of assays to detect ADA. We investigated a number of factors that may drive sensitivity and drug tolerance. We found no correlation between affinity and sensitivity and sensitivity in the presence of drug in multiple assays with two antibody-drug conjugates. Multiple factors that influenced sensitivity and drug tolerance were observed, yet these had limited overall predictive value for all investigated assay formats, PCs and compounds. Assay sensitivity and drug tolerance as studied here, are likely driven by multiple factors such as cut point confidence level, stoichiometry of PC-drug complexes and presentation of epitopes.

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