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 几种动物模型系统中的这一假设：一种是肿瘤病毒 小鼠白血病，另一个是裸无胸腺小鼠的人类肿瘤异种移植。 所使用的各种杀细胞剂是放射性同位素。 他们的 与抗体缀合时的相对治疗功效正在研究中 单独测定并比较单克隆抗体。 同位素至 所采用的包括高度杀伤肿瘤的α发射母体 放射性同位素 Pb-212 或 Bi-212。 不同螯合物的合成 正在设计实现这些目标所需的放射化学分离 并简化为临床实践。 同位素治疗的结果正在 与使用抗体偶联毒素或药物获得的结果相比 关于肿瘤生长、消退或治愈。 这些研究将为人类医学提供设计或 通过选择性靶向杀细胞剂合理治疗恶性肿瘤 肿瘤和转移瘤。 用于该项目的新螯合物已经合成并正在研究中 测试，迄今为止已证明对细胞的放射生物学研究有用 用α粒子标记的抗体杀死。