Animal Models and Assays

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，在许多模型系统中帮助评价预期用于临床研究的材料;以及B）分析临床血液、尿液、骨髓和组织活检样本。具体职能如下：1）提供所需的设施和专业知识，以评估小动物中的生物分布和成像细胞和抗体构建体，以及2）对从进入成像和治疗试验的患者获得的临床样品进行核心研究。 这个核心是一个关键的组成部分。所有抗体和T细胞构建体将在转化为临床之前进行体外和体内评价。体内分析将作为本核心的一部分，使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的帮助下进行。作为项目的一部分，将生成荧光素酶转染的肿瘤细胞系和T细胞，作为单个项目的一部分，将对抗体及其工程化构建体进行放射性标记。体内研究将在Parvin大楼的City of Hope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一种动物成像设备。它有一个Xenogen在体内生物光子成像系统（IVIS），最近已接受交付的生物空间仪器动物伽马闪烁相机。已经订购了一台用于小动物成像的Concorde Microsystems microPET@/ R4;定于2003年6月交付。该核心还将分析来自参与临床试验的患者的临床样本。将由本中心进行血液和尿液样本分析，以确定放射性标记抗体及其工程构建体的药效学。将对样品进行计数以确定药代动力学，并将通过高效液相色谱法分析所选样品以评价标记构建体的状态。本核心还将进行体外试验，以确定输注抗体和构建体的循环水平及其免疫原性。将通过ELISA或使用PerkinEImer维克托酶标仪开发的方法（使用时间分辨荧光法）进行免疫测定。

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.