title: SEC Based Method for Size Determination of Immune Complexes of Therapeutic Antibodies in Animal Matrix.
abstract: Therapeutic monoclonal antibodies (mAbs) represent a milestone in pharmacological development. Their superiority is based on the combination of high specificity, low toxicity, and long half-life that characterizes biologics. If biologics have Achilles' heel, it is their potential immunogenicity. To better understand the impact of the size of immune complexes of mAbs on anti-drug antibody (ADA) dependent adverse reactions in Macaca fascicularis, we developed an efficient high-throughput size exclusion chromatography- (SEC-) based methodology that enables analysis of the size, size distribution, and ratio of free and ADA-complexed mAb in serum allowing for assessment of formation and clearance of circulating ADA-mAb immune complexes (CIC).
authors.affiliation: AbbVie Deutschland GmbH & Co. KG, Knollstrasse 50, 67061 Ludwigshafen, Germany.
authors.forename: Marta
authors.initials: M
authors.lastname: Boysen
authors.affiliation: AbbVie Deutschland GmbH & Co. KG, Knollstrasse 50, 67061 Ludwigshafen, Germany.
authors.forename: Laura
authors.identifier: 0000-0001-7683-2338
authors.initials: L
authors.lastname: Schlicksupp
authors.affiliation: AbbVie Deutschland GmbH & Co. KG, Knollstrasse 50, 67061 Ludwigshafen, Germany.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Dreher
authors.affiliation: AbbVie Deutschland GmbH & Co. KG, Knollstrasse 50, 67061 Ludwigshafen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Loebbert
authors.affiliation: AbbVie Deutschland GmbH & Co. KG, Knollstrasse 50, 67061 Ludwigshafen, Germany.
authors.forename: Mario
authors.identifier: 0000-0002-8148-7003
authors.initials: M
authors.lastname: Richter
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D002850:Chromatography, Gel / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D057166:High-Throughput Screening Assays; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000378:metabolism; D007518:Isoantibodies / Q000276:immunology / Q000378:metabolism; D008252:Macaca fascicularis; D011485:Protein Binding; D013194:Staining and Labeling; D014116:Toxicology / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007140:Immunoglobulin Fab Fragments; D007518:Isoantibodies