Improvement of drug tolerance in immunogenicity testing by acid treatment on Biacore.
Detection of anti-drug antibodies (ADA) can be difficult, if not impossible, in the presence of drug in the sample. This is a particular concern with therapeutic monoclonal antibodies (mAbs), which have typically longer half-lives than other proteins. For detection of ADA in presence of high drug concentrations, assay choice is limited to ELISA-like methods, capable of incorporating acid dissociation procedures to separate drug-ADA immune complexes. To our knowledge, Biacore assays have not been shown to be directly compatible with acid dissociation procedures, until now. As a consequence, steps to ensure adequate clearance of the drug are prerequisite to enable sensitive detection of ADA. Here we describe the development of a novel, rapid and highly drug tolerant Biacore method that uses an acid dissociation step to detect ADA in the presence of excess drug in human serum. Removal of drug after acid treatment is not required.
Sickert
Denise
D
Novartis Pharma AG, Postfach, CH-4002, Basel, Switzerland. denise.sickert@novartis.com
Kroeger
Kerstin
K
Zickler
Christophe
C
Chokote
Edwige
E
Winkler
Barbara
B
Grenet
Jean-Michel
JM
Legay
Francois
F
Zaar
Annette
A
D000906:Antibodies / Q000097:blood* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000936:Antigen-Antibody Complex / Q000097:blood* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D006801:Humans; D006851:Hydrochloric Acid; D007158:Immunologic Techniques
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D006851:Hydrochloric Acid