Lateral Flow Immunoassays For Pharmacokinetic Dosing Of Monoclonal Antibodies

单克隆抗体药代动力学剂量的侧流免疫分析

• 批准号: 8834091
• 负责人: Dina Uzri
• 金额: $ 22.21万
• 依托单位: ABREOS BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-23 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8834091
• 关键词: Acute; Albumins; Antibodies; Benchmarking; Binding; Biological Assay; Blood; Blood specimen; Body Surface Area; Clinical; Collaborations; Data; Detection; Devices; Disease; Dose; Drug Kinetics; Drug Monitoring; Ensure; Flow Cytometry; Fluorouracil; Funding; Goals; Gold; Gold Colloid; Immunoassay; Kinetics; Laboratories; Lateral; Lead; Licensing; Ligands; Malignant Neoplasms; Measures; Methods; Monitor; Monoclonal Antibodies; Nature; Outcome; Patients; Peptides; Pharmaceutical Preparations; Pharmacology; Physicians; Population; Preparation; Reagent; Research Contracts; Running; Sampling; Scientist; Seeds; Signal Transduction; Streptavidin; Techniques; Testing; Therapeutic Monoclonal Antibodies; Trastuzumab; Tumor Burden; Variant; Whole Blood; Work; base; bevacizumab; cancer type; chemotherapy; design; improved; interest; method development; point of care; prototype; public health relevance; rituximab; tumor; validation studies

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.

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。剂量通常基于体表面积，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至达到规定的阈值可能会改善预后。类似的药代动力学剂量极大地改善了一些化疗药物。我们之前开发了用于对治疗患者中的 mAb 进行定量的实验室测定法，以及使用与给定 mAb 特异性结合的模拟表位肽进行假冒检测的侧流免疫测定法 (LFA)。对于该项目，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高于预定义阈值浓度 (CT) 的特定 mAb。将为三种最常用的单克隆抗体（曲妥珠单抗、贝伐单抗和利妥昔单抗）生产设备并进行基准测试。后者将验证接受治疗的患者的样本。我们的设备利用模拟表位肽作为免疫测定试剂的通用性质以及侧流的简单性和便利性来创建一系列可以在不同疗法中标准化的产品。