title: Development of a universal anti-adalimumab antibody standard for interlaboratory harmonization.
abstract: BACKGROUND
  Therapeutic drug monitoring of adalimumab (ADM) has been introduced recently. When no detectable ADM serum concentrations can be found, the formation of antidrug antibodies (ADA) should be investigated. A variety of assays to measure the occurrence of ADA have been developed. Results are expressed as arbitrary units or as a titration value. The aim was to develop a monoclonal antibody (MA) that could serve as a universal calibrator to quantify the amount of ADA in ADM-treated patients.
  
  
  METHODS
  Hybridoma technology was used to generate a MA toward ADM. The functionality of the MA was tested in a bridging enzyme linked immunosorbent assay (ELISA) setup and in a cell-based assay. Sera from 25 anti-tumor necrosis factor naive patients with inflammatory bowel disease were used to determine the cutoff values. Sera from 9 ADM-treated patients with inflammatory bowel disease, with undetectable serum concentrations of ADM were used to quantify the ADA response.
  
  
  RESULTS
  In this study, MA-ADM6A10, an IgG1 that can be used as a calibrator in both an ELISA to quantify the amount of binding antibodies and in a cell-based assay to quantify the amount of neutralizing antibodies, was generated. Combining the results of both assays showed that the sera with high concentrations of anti-ADM binding antibodies also had the highest neutralizing capacity.
  
  
  CONCLUSIONS
  The availability of a universal calibrator could facilitate the interlaboratory harmonization of antibody titers in patients who develop anti-adalimumab antibodies.
authors.affiliation: *Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, KU Leuven; †PharmAbs, The KU Leuven Antibody Center, University of Leuven; and ‡Department of Gastroenterology, University Hospitals Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Gils
authors.forename: Niels
authors.initials: N
authors.lastname: Vande Casteele
authors.forename: Raf
authors.initials: R
authors.lastname: Poppe
authors.forename: Marlies
authors.initials: M
authors.lastname: Van de Wouwer
authors.forename: Griet
authors.initials: G
authors.lastname: Compernolle
authors.forename: Miet
authors.initials: M
authors.lastname: Peeters
authors.forename: Els
authors.initials: E
authors.lastname: Brouwers
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.forename: Nick
authors.initials: N
authors.lastname: Geukens
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Declerck
mesh_terms: D000068879:Adalimumab; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000276:immunology; D000906:Antibodies / Q000097:blood* / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized / Q000097:blood* / Q000276:immunology; D045744:Cell Line, Tumor; D016903:Drug Monitoring / Q000379:methods; D005354:Fibrosarcoma / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007118:Immunoassay / Q000379:methods*; D007074:Immunoglobulin G / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007753:Laboratories / Q000592:standards*
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D015850:Interleukin-6; D000068879:Adalimumab