METAL CHELATE CONJUGATED MONOCLONAL ANTIBODIES FOR TUMOR DX & THERAPY

肿瘤 DX 金属螯合单克隆抗体

• 批准号: 3916579
• 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/3916579
• 关键词: antileukemic agent; antitumor antibody; athymic mouse; chelating agents; cytolysis; disease /disorder model; drug design /synthesis /production; immunoconjugates; laboratory mouse; monoclonal antibody; mouse leukemia; neoplasm /cancer immunodiagnosis; neoplasm /cancer immunotherapy; neoplasm /cancer radiodiagnosis; neoplasm /cancer radionuclide therapy; 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 several animal model systems: one is a tumor virus induced 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 to that of monoclonal antibodies alone. The isotopes now being used include the highly tumoricidal alpha emitting parent radioisotopes Pb-212 or Bi-212, as well as the beta particle emitter, Y-90. 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 of 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 used, and have thus far proven useful for radiobiology studies of cell killing with alpha particle labeled antibody and for imaging of tumors in mice. Studies of tumor imaging in patients has begun. Pre-clinical examination of Y-90 labeled antibodies for therapy are in progress.

肿瘤相关单克隆抗体是潜在的治疗药物 药物作为细胞毒剂的选择性载体来治疗恶性疾病 细胞。 我们正在几种动物模型中测试这个假设 系统：一是肿瘤病毒引起的小鼠白血病；其他 是裸无胸腺小鼠的人类肿瘤异种移植图。 所使用的各种杀细胞剂是放射性同位素。 与抗体缀合时的相对治疗功效 正在检测并与单克隆抗体进行比较 独自的。 现在使用的同位素包括高度杀伤肿瘤的同位素 α 发射母体放射性同位素 Pb-212 或 Bi-212，以及 β粒子发射器，Y-90。 不同的合成 这些所需的螯合物和放射化学分离 正在制定目标并将其付诸临床实践。 正在将同位素治疗的结果与其他结果进行比较 通过使用抗体缀合毒素或药物获得 肿瘤生长、消退或治愈。 这些研究将为人类医学设计提供基础 选择性靶向治疗恶性肿瘤的合理治疗 对肿瘤以及转移瘤的杀细胞剂。 用于该项目的新螯合物已经合成并 使用，并且迄今为止已证明对于放射生物学研究有用 使用α粒子标记抗体杀死细胞并用于成像 小鼠肿瘤。 对患者肿瘤成像的研究已经开始。 用于治疗的 Y-90 标记抗体的临床前检查是 进行中。