Immunogenicity of anti-tumor necrosis factor antibodies-toward improved methods of anti-antibody measurement

Lucien Aarden; Sigrid R Ruuls; Gertjan Wolbink

doi:10.1016/j.coi.2008.06.011

Immunogenicity of anti-tumor necrosis factor antibodies-toward improved methods of anti-antibody measurement

Curr Opin Immunol. 2008 Aug;20(4):431-5. doi: 10.1016/j.coi.2008.06.011. Epub 2008 Jul 19.

Authors

Lucien Aarden¹, Sigrid R Ruuls, Gertjan Wolbink

Affiliation

¹ 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

PMID: 18619538
DOI: 10.1016/j.coi.2008.06.011

Abstract

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.

Publication types

Review

MeSH terms

Adalimumab
Animals
Antibodies, Anti-Idiotypic / blood*
Antibodies, Anti-Idiotypic / immunology*
Antibodies, Monoclonal / immunology*
Antibodies, Monoclonal / metabolism
Antibodies, Monoclonal / therapeutic use
Antibodies, Monoclonal, Humanized
Antirheumatic Agents / immunology
Antirheumatic Agents / metabolism
Arthritis, Rheumatoid / drug therapy
Arthritis, Rheumatoid / immunology
Arthritis, Rheumatoid / metabolism
Etanercept
Humans
Immunoassay / methods*
Immunoglobulin G / immunology
Immunoglobulin G / metabolism
Immunoglobulin G / therapeutic use
Infliximab
Receptors, Tumor Necrosis Factor / immunology
Receptors, Tumor Necrosis Factor / metabolism
Receptors, Tumor Necrosis Factor / therapeutic use
Tumor Necrosis Factor-alpha / immunology*
Tumor Necrosis Factor-alpha / metabolism

Substances

Antibodies, Anti-Idiotypic
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antirheumatic Agents
Immunoglobulin G
Receptors, Tumor Necrosis Factor
Tumor Necrosis Factor-alpha
Infliximab
Adalimumab
Etanercept