title: The Effect of Induced Antibodies with Respect to Neutralization, Clearance Rate and Functional Activity in a Rabbit/Infliximab Model.
abstract: BACKGROUND
  Therapeutic antibodies are a developing field for treatment of an expanding number of inflammatory diseases, including Crohn's disease. Treatment with monoclonal antibodies is frequently hampered by development of anti-drug antibodies (ADAs) that may compromise the treatment.
  
  
  METHODS
  We addressed this issue in a rabbit model of treatment with the anti-tumor-necrosis factor alpha (TNFα) antibody, infliximab (IFX). We developed an inhibition ELISA to selectively measure absolute concentrations of neutralizing antibodies and another ELISA for measuring the concentration of functional IFX in the circulation.
  
  
  RESULTS
  We found that the concentration of functional IFX was inversely proportional to the concentration of neutralizing antibodies.
  
  
  CONCLUSIONS
  Administration of IFX to rabbits showed diversity in immune responses/tolerance toward IFX, corresponding to responses observed in patients. The applied assay technology is easily adapted to human plasma samples and/or other therapeutic antibodies, including fully humanized antibodies, for which immunogenicity also is observed.
authors: Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors: Maiken Lumby
authors: ML
authors: Henriksen
authors: Department of Gastroenterology, Odense University Hospital, Odense, Denmark.
authors: Ane
authors: A
authors: Teisner
authors: Department of Gastroenterology, Odense University Hospital, Odense, Denmark.
authors: Jens
authors: J
authors: Kjeldsen
authors: Department of Experimental Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Otto
authors: O
authors: Kalliokoski
authors: Department of Experimental Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Jann
authors: J
authors: Hau
authors: Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark shansen@health.sdu.dk.
authors: Soren Werner Karlskov
authors: SW
authors: Hansen
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage* / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000009:adverse effects; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D000069285:Infliximab / Q000008:administration & dosage* / Q000009:adverse effects; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
keywords: Therapeutic monoclonal antibodies; immunogenicity; infliximab