1. Identification and inhibition of drug target interference in immunogenicity assays.
- Author
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Zhong ZD, Dinnogen S, Hokom M, Ray C, Weinreich D, Swanson SJ, and Chirmule N
- Subjects
- Angiopoietins blood, Angiopoietins genetics, Angiopoietins immunology, Animals, Antibodies, Monoclonal genetics, Antibodies, Monoclonal immunology, Biological Assay, Clinical Trials as Topic, Female, Humans, Immunoassay methods, Immunoglobulin Fc Fragments genetics, Immunoglobulin Fc Fragments immunology, Male, Mice, Neoplasms drug therapy, Neoplasms genetics, Neoplasms immunology, Neovascularization, Pathologic drug therapy, Neovascularization, Pathologic immunology, Peptides genetics, Peptides immunology, Receptor, TIE-2 antagonists & inhibitors, Receptor, TIE-2 genetics, Receptor, TIE-2 immunology, Receptor, TIE-2 metabolism, Sensitivity and Specificity, Antibodies, Monoclonal chemistry, Drug Interactions, Immunoglobulin Fc Fragments analysis, Neoplasms blood, Neovascularization, Pathologic blood, Peptides analysis
- Abstract
A well-designed anti-drug antibody (ADA) immunoassay is critical for appropriately monitoring the immunogenicity profile of a therapeutic protein during its development. AMG 386 is a peptide-Fc fusion protein that inhibits angiogenesis by preventing the interaction of angiopoietins with the Tie2 receptor. In bridging immunoassays for ADA, interference by the drug target, present in the assay sample, can result in false positive antibody detection. We used a statistical design-of-experiments approach to identify angiopoietin interference in bridging immunoassays of anti-AMG 386 antibodies. We also demonstrated that a high-affinity monoclonal antibody, directed against an epitope on angiopoietin that competes with AMG 386 binding, could inhibit the angiopoietin interference while preserving the detection of ADA. This report describes the development and validation of methodologies for evaluating and addressing drug target interference in bioanalytical assays that involve interactions between drug, ADA, immune complexes, and drug target., (Copyright 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
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