Lateral Flow Immunoassays For Pharmacokinetic Dosing Of Monoclonal Antibodies

描述(申请人提供)：单抗(MAb)用于治疗多种癌症和其他疾病。剂量通常基于身体表面积，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，循环抗体最终谷水平较低的患者预后较差，这表明动态监测血液抗体水平并进行治疗，直到达到规定的阈值可能会改善预后。相似的药动学剂量极大地改进了一些化疗药物。我们之前已经开发了实验室检测方法，用于定量治疗患者的mAb，以及侧向流动免疫分析(LFA)，用于使用与给定mAb特异结合的模拟表位多肽进行假冒检测。对于这个项目，我们建议开发原型LFA设备，该设备可以确定血液样本中是否存在超过预定阈值浓度(CT)的特定mAb。将生产三种最常用的单抗：曲妥珠单抗、贝伐单抗和利妥昔单抗，并对其进行基准测试。后者将在接受治疗的患者的样本上进行验证。我们的设备利用模拟表位多肽作为免疫分析试剂的普遍性质，以及横向流动的简单和方便，创建了一系列可以在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.