Lateral Flow Immunoassays For Pharmacokinetic Dosing Of Monoclonal Antibodies

描述（由申请人提供）：单克隆抗体（mAb）用于治疗多种癌症和其他疾病。给药通常基于体表面积，但群体药代动力学（PK）数据表明患者之间存在相当大的差异。此外，越来越多的证据表明，循环抗体最终谷值水平较低的患者结局较差，这表明动态监测血液抗体水平和治疗直至获得定义的阈值可能会改善结局。相似的药代动力学给药大大改善了一些化疗药物。我们之前已经开发了用于在治疗患者中定量mAb的实验室测定和用于使用特异性结合给定mAb的微肽进行假冒检测的侧流免疫测定（LFA）。对于这个项目，我们建议开发原型LFA设备，可以确定给定的mAb是否存在于血液样本中高于预定义的阈值浓度（CT）。将生产器械并对三种最常用的mAb进行基准测试：曲妥珠单抗、贝伐珠单抗和利妥昔单抗。后者将对来自治疗患者的样本进行验证。我们的设备利用了作为免疫测定试剂的米托肽的一般性质以及横向流动的简单性和便利性，以创建一系列可以在各种治疗中标准化的产品。

DESCRIPTION (provided by applicant): Monoclonal antibodies (mAb) are used to treat a variety of cancers and other diseases. Dosing is typically based on body surface area, but population pharmacokinetic (PK) data suggests considerable variation across patients. Furthermore, there is growing evidence that patients with low final trough levels of circulating antibody have a poorer outcome, suggesting that dynamic monitoring of blood antibody levels and treating until a defined threshold is obtained may improve outcomes. Similar pharmacokinetic dosing has greatly improved some chemotherapy agents. We have previously developed laboratory assays for the quantitation of mAb in treated patients and lateral flow immunoassays (LFA) for counterfeit detection using mimetope peptides that specifically bind to a given mAb. For this project, we propose to develop prototype LFA devices that can determine if a given mAb is present in a blood sample above a predefined threshold concentration (CT). Devices will be produced and benchmarked for the three most commonly used mAb: trastuzumab, bevacizumab, and rituximab. The latter will validate on samples from treated patients. Our devices leverage the generalized nature of mimetope peptides as an immunoassay reagent as well as the simplicity and convenience of lateral flow to create a line of products that can be standardized across therapies.