CORE--ANALYTICAL AND ANIMAL

核心D(分析和动物核心)的作用是为 三个领域的项目1、2和3： 1)进行抗CEA临床前评估的体外试验 在项目2中开发的构建和免疫融合。这些包括：a) 抗CEA检测免疫反应性，b)IL-2和γ-干扰素生物检测 和酶联免疫吸附试验，以表征和评估功能活性 C)动物肿瘤标本的CEA免疫组织化学。 2)进行动物(小鼠)研究，以进行临床前评估 项目中开发的新型抗CEA生物工程构建物和螯合物 2和3.这些包括：a)生物分布/成像研究 用I-123或In-111，b标记的中分子量构建体) 新型抗癌胚抗原螯合物的生物分布研究 用In-111或铜-标记的抗体构建物，c)研究评估 工程免疫融合的生物分布和功能活性 构建物(微体-IL-2和单链抗体-γ-干扰素免疫融合)，d) 评估90Y标记结构的治疗效果的研究，以及 E)所有临床接种的大量抗体之前的生物分布研究 计划中的临床试验。 3)对患者的临床样本进行核心研究 参与了项目1中的成像和治疗试验。这些研究 包括：a)对血、尿和组织进行In-111、90-Y和I-123计数 活检样本，b)In-111和90-Y骨髓样本计数，c) 对血液样本进行人类抗嵌合抗体和抗录音带检测， 以及d)血样和尿样的高效液相色谱分析。

The role of Core D (Analytical and Animal Core) is to provide support to Projects 1, 2, and 3 in three areas: 1) To perform in vitro assays for pre-clinical evaluation of anti-CEA constructs and immunofusions developed in Project 2. These include: a) anti-CEA assays immunoreactivity, b) IL-2 and gamma-interferon bioassays and elisa assays to characterize and assess functional activity of the immunofusions, and c) CEA immunohistochemistry of animal tumor samples. 2) To perform animal (murine) studies for pre-clinical evaluation of novel anti-CEA bioengineered constructs and chelates developed in Projects 2 and 3. These include: a) biodistribution/imaging studies evaluating intermediate molecular weight constructs labeled with I-123 or In-111, b) biodistribution studies evaluating novel chelates conjugagted to anti-CEA antibody constructs labeled with In-111 or Cu-64, c) studies evaluating biodistribution and functional activity of engineered immunofusion constructs (minibody-IL-2 and scFv-gamma-interferon immunofusions), d) studies evaluating the therapeutic effects of 90Y labeled constructs, and e) biodistribution studies of all clinical vialed lots of antibody prior to planned clinical trials. 3) to perform core studies on clinical samples obtained from patients entered on imaging and therapy trials in project 1. These studies include: a) In-111, 90-Y and I-123 counting of blood, urine, and tissue biopsy samples, b) In-111 and 90-Y counting of bone marrow samples, c) human anti-chimeric antibody and anti-audiotape assays on blood samples, and d) HPLC analysis of blood and urine samples.