Indirect assessment of neutralizing anti-drug antibodies utilizing pharmacokinetic assay data
| Autor: | Jessica Ortiz, Sergio Sanchez, Christian Vettermann, Hannah P. Victor, Timothy G. Heath, Mark Ma, Shalini Gupta, Stephanie A. Lee |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Drug Direct assessment media_common.quotation_subject Immunology Pharmacology 03 medical and health sciences Pharmacokinetics Drug tolerance Immunology and Allergy Medicine Humans Dosing media_common biology business.industry Immunogenicity Serum concentration Antibodies Neutralizing 030104 developmental biology Pharmaceutical Preparations biology.protein Antibody business Drug Antagonism |
| Zdroj: | Journal of immunological methods. 429 |
| ISSN: | 1872-7905 |
| Popis: | Neutralizing anti-drug antibodies (NAbs) can adversely impact efficacy and safety of biologic therapeutics. However, current assay formats to detect NAbs are limited in their use during the dosing phase due to interference by circulating drug, resulting in low drug tolerance. To improve the drug tolerance for NAb detection, an alternative approach for indirect NAb (iNAb) assessment was developed and qualified that uses a combination of pharmacokinetic (PK) assays to measure the serum concentrations of free and total drug. It is demonstrated that the ratio of free to total drug concentrations, referred to as F/T ratio, is a novel PK parameter that can indicate neutralizing activity in test samples. The iNAb assessment correctly identified NAb-positive samples with high drug concentrations that led to false negative results in a conventional NAb assay. Moreover, iNAb reliably distinguished between NAbs and non-neutralizing anti-drug antibodies over a wide range of concentrations. A proposal on how to deploy iNAb assessment within a broader immunogenicity testing strategy is presented. |
| Databáze: | OpenAIRE |
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