Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, New York, 10591, USA.
AAPS J. 2020 Aug 17;22(5):112. doi: 10.1208/s12248-020-00497-2.
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.
中和抗体（NAb）检测通常比药物谷浓度具有更低的药物耐受性（DT），可能会低估 NAb 的发生率。为了提高 DT，将药物特异性蛋白偶联到磁珠上以耗尽样品中的药物。为了避免残留干扰，选择了不会干扰 NAb 检测的药物特异性蛋白，如靶标或非阻断性抗药物抗体。通过药物耗尽步骤，两种竞争性配体结合 NAb 检测的 DT 提高了 10 倍以上。对药物水平升高的抗药物抗体阳性临床样本的分析表明，如果没有药物耗尽步骤，NAb 的发生率会被低估。然而，这些 NAb 阳性样本的滴度较低，对药物浓度没有影响。
