Immunogenicity of anti-tumor necrosis factor antibodies-toward improved methods of anti-antibody measurement.
To date, millions of people have been treated with therapeutic monoclonal antibodies (TmAbs) for various indications. It is becoming increasingly clear that TmAbs can be immunogenic, which may reduce efficacy or induce adverse effects. Over the years, the importance of antibody formation has been questioned and sometimes minimized, as few antibody responses to TmAbs (HACA or HAHA) were reported. However, the methods to detect and quantify such antibodies used in the past have been problematic. Only recently, methods have been developed that have adequate sensitivity and are not seriously disturbed by false-positive reactions caused by rheumatoid factors, natural antibodies to Fab or F(ab')2 fragments, or Fc interactions of IgG4. The large number of treated patients, in combination with these new assays, presents a unique opportunity to study the anti-antibody immune response in man, possibly allowing us to manipulate immunogenicity in the future.
Aarden
Lucien
L
Sanquin Research at Central Laboratory for Blood Transfusion and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Plesmanlaan 125, Amsterdam, The Netherlands. l.aarden@sanquin.nl
Ruuls
Sigrid R
SR
Wolbink
Gertjan
G
D000068879:Adalimumab; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood* / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000276:immunology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D000068800:Etanercept; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D000069285:Infliximab; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept