Animal Models and Assays

动物模型和测定

• 批准号: 6992465
• 负责人: DAVID MORRIS COLCHER
• 金额: $ 11.17万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-02 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6992465
• 关键词: Hodgkin' s disease; bioimaging /biomedical imaging; biomedical facility; biopsy; bone marrow exam; clinical research; disease /disorder model; human tissue; immunologic assay /test; laboratory mouse; model design /development; neoplasm /cancer therapy; nonHodgkin' s lymphoma; nonhuman therapy evaluation; pharmacokinetics; urinalysis

This core has two main functions: a) to help evaluate the materials that are intended for clinical studies, in a number of model systems, using the advanced animal imaging instrumentation available at the COH; and b) the analysis of clinical blood, urine, bone marrow, and tissue biopsy samples. The Specific Functions are: 1) To provide the needed facilities and expertise for evaluating the biodistribution and imaging cells and antibody constructs in small animals, and 2) To perform core studies on clinical samples obtained from patients entered on imaging and therapy trials. This Core is a critical component. All antibody and T-cell constructs will be evaluated in vitro and in vivo prior to translation into the clinic. The in vivo analysis will be performed as part of this Core using the expertise of the Core's personnel. Animal biodistribution and imaging studies will be performed using the Core personnel with help as needed from the individual projects. Luciferase transfected tumor cell lines and T-cells will be generated as part of the projects and antibodies and their engineered constructs will be radiolabeled as part of the individual projects. The in vivo studies will be performed in the City of Hope Animal Resource Center in the Parvin building. The City of Hope National Medical Center and Beckman Research institute is developing an animal imaging facility. It has a Xenogen in vivo biophotonic imaging system (IVIS) and has recently accepted delivery of a Biospace Instruments animal gamma scintillation camera. A Concorde Microsystems microPET@/ R4 for small animals imaging has been ordered; it is due to be delivered in June 2003. This core will also analyze clinical samples from patients participating in the clinical trials. Analysis of blood and urine samples to determine the pharmacodynamics of the radiolabeled antibodies and their engineered constructs will be performed by this Core. Samples will be counted to determine the pharmacokinetics and selected samples will be analyzed by high performance liquid chromatography to evaluate the status of the labeled construct. In vitro assays to determine circulating levels of infused antibodies and constructs, as well as their immunogenicity, will also be performed by this Core.. Immunoassays will be performed by ELISA or using methods developed using the PerkinEImer VICTOR plate reader using time-resolved fluorometry.

该核心有两个主要功能： a) 使用 COH 提供的先进动物成像仪器，帮助在许多模型系统中评估用于临床研究的材料； b) 临床血液、尿液、骨髓和组织活检样本的分析。具体职能是：1) 提供评估小动物体内生物分布、成像细胞和抗体构建体所需的设施和专业知识，2) 对从参加成像和治疗试验的患者获得的临床样本进行核心研究。 该核心是一个关键组件。所有抗体和 T 细胞构建体在转化为临床之前都将在体外和体内进行评估。体内分析将作为该核心的一部分，利用核心人员的专业知识进行。动物生物分布和成像研究将由核心人员在各个项目需要的帮助下进行。作为项目的一部分，将产生荧光素酶转染的肿瘤细胞系和 T 细胞，并且作为各个项目的一部分，抗体及其工程构建体将被放射性标记。体内研究将在帕尔文大楼的希望之城动物资源中心进行。希望之城国家医疗中心和贝克曼研究所正在开发动物成像设施。它拥有 Xenogen 体内生物光子成像系统 (IVIS)，最近已接受 Biospace Instruments 动物伽马闪烁相机的交付。已订购用于小动物成像的 Concorde Microsystems microPET@/ R4；它预计于 2003 年 6 月交付。该核心还将分析参与临床试验的患者的临床样本。该核心将通过分析血液和尿液样本来确定放射性标记抗体及其工程构建体的药效学。对样品进行计数以确定药代动力学，并通过高效液相色谱分析选定的样品以评估标记构建体的状态。该核心也将进行体外测定，以确定输注抗体和构建体的循环水平及其免疫原性。免疫测定将通过 ELISA 或使用使用时间分辨荧光测定法的 PerkinEImer VICTOR 读板仪开发的方法进行。