METAL CONJUGATED MONOCLONAL ANTIBODIES FOR TUMOR DIAGNOSIS AND THERAPY

用于肿瘤诊断和治疗的金属偶联单克隆抗体

• 批准号: 4692108
• 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/4692108
• 关键词: antitumor antibody; chelating agents; disease /disorder model; drug design /synthesis /production; immunoconjugates; monoclonal antibody; mouse leukemia; neoplasm /cancer immunodiagnosis; neoplasm /cancer radiodiagnosis; neoplasm /cancer radionuclide therapy; neoplasm /cancer transplantation; radiopharmacology; viral leukemia

Tumor-associated monoclonal antibodies are potential therapeutic agents as selective carriers of cytotoxic agents to malignant cells. We are testing this hypothesis in serveral animal model systems: one is a tumor virus leukemia of mice, another is human tumor xenographs in nude athymic mice. The various cytocidal agents being employed are radioisotopes. Their relative therapeutic efficacy when conjugated to antibodies is being assayed and compared that of monoclonal antibodies alone. The isotopes to be employed include the highly tumoricidal alpha emitting parent radioisotopes Pb-212 or Bi-212. The syntheses of different chelates and radiochemical separations required for these objectives are being devised and reduced to clinical practice. Results from isotopic therapy are being compared with those obtained by use of antibody conjugated toxins or drugs with respect to tumor growth, regression or cure. These studies will provide for human medicine a basis for design or rational therapy of malignancies by selectively targeting cytocidal agents to tumors as well as metastases. New chelates for use in this project have been synthesized and are in testing, and have thus far proven useful for Radiobiology studies of cell killing with alpha particle labeled antibody.

肿瘤相关单抗是潜在的治疗药物 细胞毒剂对恶性细胞的选择性载体。我们正在测试 在几个动物模型系统中的这个假设：一个是肿瘤病毒 另一种是人肿瘤裸鼠移植瘤。 所使用的各种细胞杀伤剂是放射性同位素。他们的 与抗体结合时的相对治疗效果正在 对单抗进行检测和比较。所需的同位素 包括具有高度杀瘤活性的阿尔法发射母体 放射性同位素铅-212或铋-212。不同络合物的合成及应用 这些目标所需的放射化学分离正在设计中。 并简化为临床实践。同位素治疗的结果是 与使用抗体结合的毒素或药物获得的结果进行比较 关于肿瘤的生长、消退或治愈。 这些研究将为人类医学提供设计或 选择靶向细胞杀伤剂合理治疗恶性肿瘤 无论是肿瘤还是转移。 用于该项目的新的螯合物已经合成，并已在 测试，到目前为止已被证明对细胞的放射生物学研究有用 用α粒子标记抗体进行杀伤。