Drug Removal Strategies in Competitive Ligand Binding Neutralizing Antibody (NAb) Assays: Highly Drug-Tolerant Methods and Interpreting Immunogenicity Data
| Autor: | Camille Georgaros, Giane Sumner, Albert Torri, Elif Kabuloglu Karayusuf, Michael A Partridge, Gary Shyu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Drug
biology Chemistry Immunogenicity media_common.quotation_subject Pharmacology toxicology Antibodies Monoclonal Pharmaceutical Science Pharmacology Antibodies Neutralizing 030226 pharmacology & pharmacy Drug levels 03 medical and health sciences Titer 0302 clinical medicine Pharmaceutical Preparations Drug tolerance 030220 oncology & carcinogenesis Immunogenetics biology.protein Humans Antibody Neutralizing antibody media_common |
| Zdroj: | The AAPS Journal. 22 |
| ISSN: | 1550-7416 |
| DOI: | 10.1208/s12248-020-00497-2 |
| Popis: | Neutralizing anti-drug antibody (NAb) assays often have lower drug tolerance (DT) than trough drug concentrations, potentially under-estimating NAb incidence. To improve DT, drug-specific proteins were coupled to magnetic beads to deplete drug in the sample. To avoid interference from carryover, drug-specific proteins that did not interfere in the NAb assay, such as target or non-blocking anti-drug antibodies, were selected. With the drug depletion step, DT improved by > 10-fold in two competitive ligand binding NAb assays. Analysis of anti-drug antibody positive clinical samples with elevated drug levels demonstrated that NAb incidence was under-estimated without the drug depletion step. However, these NAb-positive samples had low titer and no impact on drug concentrations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink