METAL CHELATE CONJUGATED MONOCLONAL ANTIBODIES FOR TUMOR DIAGNOSIS AND THERAPY

用于肿瘤诊断和治疗的金属螯合单克隆抗体

• 批准号: 5201255
• 负责人: O A GANSOW
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5201255
• 关键词: Primates; antitumor antibody; bismuth; chelating agents; cytotoxicity; diethylenetriaminepentaacetate; disease /disorder model; immunoconjugates; metastasis; monoclonal antibody; neoplasm /cancer immunodiagnosis; neoplasm /cancer immunotherapy; neoplasm /cancer radiodiagnosis; neoplasm /cancer radionuclide therapy; radionuclide diagnosis; radionuclide imaging /scanning; radionuclides; radiopharmacology; yttrium

Tumor associated monoclonal antibodies are potential therapeutic agents as selective carriers of cytotoxic agents to malignant cells. We are testing this hypothesis in several animal model systems. The cytocidal agents being employed are various radionuclides. Their relative efficacy when conjugated to monoclonal antibodies is being assayed and compared to that of monoclonal antibodies alone or conjugated to toxins. The several radionuclides chosen for study span the range of radionuclidic properties available. Recent research has focused on clinical use of Yttrium-90, and on completing preclinical studies with the alpha particle emitting nuclides Bismuth-212 and Bismuth-213. Most recently, we have installed a Hot Cell in the radiation laboratory in order tb make high level activity (>10 mCi) doses of antibodies labeled with the Bismuth-212 alpha particle emitter. Studies of toxicity of Bismuth-212-antibody doses is underway in monkeys. Currently, 4 mCi doses have shown almost no blood or other toxicity. Based on these data, an IND for treatment of leukemia patients will be constructed. Studies like these are providing for human medicine a basis for design of rational therapies of malignancies by selectively targeting cytocidal agents to tumors, as well as metastases and will in addition allow improved diagnostic imaging of malignancies.

肿瘤相关单克隆抗体是潜在的治疗药物 恶性细胞的细胞毒剂的选择性载体。 我们正在测试 这一假设在几个动物模型系统中得到了证实。 所使用的杀细胞剂是各种放射性核素。 他们的 与单克隆抗体缀合时的相对功效正在研究中 与单独或缀合的单克隆抗体进行测定和比较 到毒素。 选择用于研究的几种放射性核素的范围 可用的放射性核素特性。 最近的研究重点是 Yttrium-90 的临床应用，以及 完成α粒子发射核素的临床前研究 铋 212 和铋 213。 最近，我们在辐射实验室安装了一个热室 订购 tb 制作高水平活性 (>10 mCi) 剂量的标记抗体 与 Bismuth-212 α 粒子发射器。 毒性研究 Bismuth-212-抗体剂量正在猴子身上进行。 目前，4 mCi 剂量 几乎没有表现出血液或其他毒性。 根据这些数据，IND 将建造用于治疗白血病患者的医院。 诸如此类的研究为人类医学提供了设计基础 通过选择性靶向杀细胞剂来合理治疗恶性肿瘤 肿瘤以及转移的药物，此外还允许 改进了恶性肿瘤的诊断成像。