title: Detection of antidrug antibodies against human therapeutic antibodies lacking Fc-effector functions by usage of soluble Fcγ receptor I.
abstract: OBJECTIVE
  Bridging immunoassays for the detection of antidrug antibodies (ADAs) are limited to detection of bivalent molecules and are prone to interference by drug and soluble targets. Hence, alternative approaches for ADA detection are desired. Materials & methods: A novel ADA assay with secondary Fc detection using human soluble Fcγ receptor I (hsFcγRI) was established and compared with standard bridging assay.
  
  
  RESULTS
  Both assays showed consistent results in human and cynomolgus monkey samples. In contrast to the bridging assay, the hsFcγRI-based assay was insensitive to the presence of oligomeric targets and appeared to have better drug tolerance.
  
  
  CONCLUSIONS
  The hsFcγRI-based ADA assay can serve as alternative screening assay or as orthogonal confirmation method for preclinical and clinical immunogenicity testing of IgG therapeutics lacking Fc effector functions.
authors: Pharmaceutical Sciences, Pharma Research & Early Development, Roche Innovation Center Munich, Nonnenwald 2, 82377 Penzberg, Germany.
authors: Uwe
authors: U
authors: Wessels
authors: Pharmaceutical Sciences, Pharma Research & Early Development, Roche Innovation Center Munich, Nonnenwald 2, 82377 Penzberg, Germany.
authors: Alexander
authors: A
authors: Poehler
authors: Pharmaceutical Sciences, Pharma Research & Early Development, Roche Innovation Center Munich, Nonnenwald 2, 82377 Penzberg, Germany.
authors: Miriam
authors: M
authors: Moheysen-Zadeh
authors: Pharmaceutical Sciences, Pharma Research & Early Development, Roche Innovation Center Munich, Nonnenwald 2, 82377 Penzberg, Germany.
authors: Markus
authors: M
authors: Zadak
authors: Pharmaceutical Sciences, Pharma Research & Early Development, Roche Innovation Center Munich, Nonnenwald 2, 82377 Penzberg, Germany.
authors: Roland F
authors: RF
authors: Staack
authors: Roche Pharma Research & Early Development, Roche Innovation Center Zurich, Wagistrasse 18, 8952 Schlieren, Switzerland.
authors: Pablo
authors: P
authors: Umana
authors: Pharmaceutical Sciences, Pharma Research & Early Development, Roche Innovation Center Munich, Nonnenwald 2, 82377 Penzberg, Germany.
authors: Julia
authors: J
authors: Heinrich
authors: Pharmaceutical Sciences, Pharma Research & Early Development, Roche Innovation Center Munich, Nonnenwald 2, 82377 Penzberg, Germany.
authors: Kay
authors: K
authors: Stubenrauch
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000936:Antigen-Antibody Complex; D005260:Female; D006801:Humans; D007118:Immunoassay; D008252:Macaca fascicularis; D008297:Male; D011485:Protein Binding; D018121:Receptors, Cytokine / Q000276:immunology; D017452:Receptors, IgG / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D020349:Surface Plasmon Resonance
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; C498762:CRLF2 protein, human; D018121:Receptors, Cytokine; D017452:Receptors, IgG; D011994:Recombinant Proteins
keywords: ELISA; FcγRI; antidrug antibody; drug interference; immunogenicity; safety assessment; suppressed Fc effector functions; target interference