RADIOPHARMACY AND ASSAYS

放射药物和分析核心(核心B)的主要目标是支持项目1：放射免疫治疗：临床研究，项目2：针对治疗的抗CEA抗体，以及项目3：CEA靶向免疫治疗，通过提供专业知识和设施来制备放射性标记抗体以及治疗和成像试剂的质量控制。Y-90标记的嵌合/人源化T84.66抗CEA抗体将用于结肠癌和肺癌的临床试验，Y-90标记的赫赛汀将用于希望城国家医学中心的乳腺癌患者，铟-111标记的嵌合/人源化T84.66抗体、阿瓦斯丁和赫赛汀将用于成像和剂量学研究。放射性药房将通过提供放射性标记抗体来支持项目1，并将为这些试剂提供质量控制。 该中心还负责对患者(和动物)的血液样本进行分析，以评估给药产品的血液清除性和稳定性。患者血清样本也被分析，以监测患者对注射的抗体构建体的免疫反应。 Core B还对所有抗体、工程抗体、化学修饰抗体和半抗原进行放射性标记，以供临床前在体外和体内使用。放射性药剂的制备过程包括络合、偶联化学和偶联以及抗体的放射性标记。作为其核心活动的一部分，放射性制药公司还为临床级材料开发单抗构建结合方法，这些材料将在cGMP设施中制备，用于第一阶段试验。 核心B将与所有三个项目以及本申请中的核心A、C、D和E相关联。

The principal objective of the Radiopharmacy and Assays Core (Core B) is to support Project 1: Radioimmunotherapy: Clinical Studies, Project 2: Pretargeting with anti-CEA Antibodies for Therapy, and Project 3: CEA Targeted Immunotherapeutics by providing expertise and facilities to prepare radiolabeled antibodies and quality control for therapeutic and imaging reagents. Yttrium-90 radiolabeled chimeric/humanized T84.66 anti-CEA antibody will be used in the clinical trials for colon and lung cancer satients, and yttrium-90 radiolabeled Herceptin will be used in breast cancer patients at the City of Hope National Medical Center, lndium-111 radiolabeled chimeric/humanized T84.66 antibody, Avastin and Herceptin will be used for imaging and dosimetry studies. The radiopharmacy will support Project 1 by providing the radiolabeled antibodies and will provide quality control for these reagents. This Core is also responsible for the analysis of patient (and animal) blood samples to evaluate the blood clearance and stability of the administered products. Patient sera samples are also analyzed to monitor the patient's immune response to the injected antibody constructs. Core B also performs the radiolabeling of all the antibodies, engineered antibodies, chemically modified antibodies and haptens for preclinical in vitro and in vivo use. Procedures involved in preparation of the radiopharmaceutical agents include chelate conjugate chemistry and conjugation as well as the antibody radiolabeling. As part of its core activity the Radiopharmacy also develops the monoclonal antibody construct conjugation methodologies for the clinical grade materials to be prepared in the cGMP facility for the Phase I trials. Core B will be associated with all three Projects as well as Cores A, C, D and E in this application.