title: Improvement of drug tolerance in immunogenicity testing by acid treatment on Biacore.
abstract: 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.
authors.affiliation: Novartis Pharma AG, Postfach, CH-4002, Basel, Switzerland. denise.sickert@novartis.com
authors.forename: Denise
authors.initials: D
authors.lastname: Sickert
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kroeger
authors.forename: Christophe
authors.initials: C
authors.lastname: Zickler
authors.forename: Edwige
authors.initials: E
authors.lastname: Chokote
authors.forename: Barbara
authors.initials: B
authors.lastname: Winkler
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Grenet
authors.forename: Francois
authors.initials: F
authors.lastname: Legay
authors.forename: Annette
authors.initials: A
authors.lastname: Zaar
mesh_terms: 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
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D006851:Hydrochloric Acid