Homogeneous assay for monoclonal antibody detection in serum

血清中单克隆抗体检测的均相测定

• 批准号: 8007141
• 负责人: Manuel E Ruidiaz
• 金额: $ 3.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-22 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8007141
• 关键词: Accounting; Acute; Address; Affinity; Antibodies; Antibody Therapy; Antigens; Antineoplastic Agents; Avidity; Binding; Biological; Biological Assay; Biology; Blood specimen; Cancer Patient; Chronic Lymphocytic Leukemia; Clinical Research; Clinical Treatment; Complex; Cystine; Detection; Development; Devices; Diagnostic or Prognostic Factor; Disease; Disulfide Linkage; Dose; Drug Kinetics; Effectiveness; Energy Transfer; Fluorescence; Fluorescence Polarization; Goals; Health; Individual; Injection of therapeutic agent; Label; Lead; Lysine; Malignant Neoplasms; Measurement; Measures; Medical; Medicine; Metabolism; Monoclonal Antibodies; Morphologic artifacts; Nature; Overdose; Patients; Peptide antibodies; Peptides; Phage Display; Pharmaceutical Preparations; Pharmacotherapy; Phase; Probability; Reagent; Regimen; Reporter; Reporting; Research; Resistance; Rotation; Route; Sampling; Schedule; Scheme; Serum; Solutions; Specificity; Speed; System; Techniques; Technology; Testing; Therapeutic Agents; Tumor Burden; Uncertainty; alemtuzumab; base; cancer therapy; design; dosage; drug development; fluorophore; improved; mimetics; model development; novel; peptide P; point of care; pre-clinical; response; rituximab; technology development; therapeutic protein; tumor

DESCRIPTION (provided by applicant): The long term goal of this application is to develop a device to provide rapid point of care analysis of the state of antibodies drugs within patient serum. Antibodies are widely used in a variety of applications, as therapeutic agents and reagents in biological assays. The ability to detect and quantify antibodies is a key aspect in many of their applications. Detection of antibodies and other protein therapeutics in a biological sample is critical in medical applications requiring determination of diagnostic and/or prognostic factors. However, determining the pharmacokinetics of a particular antibody can be problematic, especially when the detection is performed against a high background, as in a biological sample. There are two key applications. (1) Dosing schedules and routes of administration for antibody drugs are developed with many uncertainties and are often refined through pre-clinical and clinical studies where the need for simple and reliable pharmacokinetic assays is acute. The specific biology of a given antibody target can also lead to additional complications from the conventional dose escalation paradigm. (2) Antibody cancer drugs would be more economical and safer if the dose for each patient could be adjusted based on the antibody levels detected in the serum of the patient after each injection since the great variability in patient metabolism and tumor load is not captured in traditional dosage schemes. An enhanced detection system has been developed that can rapidly determine the concentration of antibody drugs present from blood samples. This research will focus on the development of this technology to further improve the assay in terms of reliability and sensitivity. Alemtuzumab (anti-CD52) will be used as a development model for assay refinement. It is currently used commonly in patients with chronic lymphocytic leukemia (CLL). The research will consist of three phases. 1) Development of a first order homogeneous assay for measurement of antibody. 2) Development of a novel enhancement technique for high sensitivity detection. 3) Determination and implementation of an assay kit to allow for point of care detection and analysis.

描述（由申请人提供）：本申请的长期目标是开发一种设备，以提供患者血清内抗体药物状态的快速护理分析。抗体被广泛用于各种应用中，作为生物测定中的治疗剂和试剂。检测和量化抗体的能力是其许多应用中的关键方面。在需要确定诊断和/或预后因素的医学应用中，在生物样本中检测抗体和其他蛋白质疗法至关重要。但是，确定特定抗体的药代动力学可能是有问题的，尤其是当在高背景进行检测时（如生物样品中）。有两个关键应用程序。 （1）抗体药物的剂量时间表和给药途径是许多不确定性开发的，并且通常通过临床前和临床研究来完善，在临床前和临床研究中，对简单可靠的药代动力学测定的需求是急性的。给定抗体靶标的特定生物学也可能导致常规剂量升级范式的其他并发症。 （2）如果可以根据注射后患者血清中检测到的抗体水平调整每个患者的剂量，则抗体癌症药物将更加经济，更安全。已经开发了增强的检测系统，该系统可以快速确定血液样本中存在的抗体药物的浓度。这项研究将重点放在该技术的开发上，以进一步改善可靠性和敏感性。 Alemtuzumab（抗CD52）将用作测定改进的开发模型。目前，它通常用于慢性淋巴细胞性白血病（CLL）的患者。该研究将由三个阶段组成。 1）开发用于测量抗体的一阶均质测定法。 2）开发一种新型增强技术，用于高灵敏度检测。 3）确定和实施测定套件以允许进行护理点检测和分析。