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: 6123650
• 负责人: MARTIN W BRECHBIEL
• 金额: --
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 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/6123650
• 关键词: Primates; antitumor antibody; bismuth; chelating agents; cytotoxicity; diethylenetriaminepentaacetate; disease /disorder model; immunoconjugates; laboratory mouse; 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 (mAb) are potential therapeutic agents as selective carriers of cytotoxic agents to malignant cells. This hypothesis is tested in animal model systems with mAbs directed toward antigens associated with a variety of malignancies. The cytocidal agents being employed are various radionuclides. Their relative efficacy when conjugated to monoclonal antibodies is assayed and compared to that of monoclonal antibodies alone, radiolabeled with I-131, or conjugated to toxins. The several radionuclides chosen for study span the range of radionuclidic properties available thereby assaying the effects of energy of emission, half-life, and physical characteristics of emission. Research continues to focus on expanding clinical use of Y-90 and on completing pre-clinical studies with the alpha-particle emitting radionuclides Bi-212, Bi-213, and At-211. The ongoing clinical trials at the NIH currently employ the second generation bifunctional chelating agent 1B4M-DTPA (aka MX-DTPA) for sequestering Y-90. Recent results in chelate design technology have revealed an in vivo dependency of the absolute configuration of the bifunctional chelating agent to optimize radio-metal complex stability. Due to these results, all current efforts involving In-111, lanthanide ions, and Bi-212,213 have been converted to being performed with CHX-A'' DTPA. Future clinical trials, such as those being planned with mAb 7G7 in conjunction with humanized anti-Tac for the treatment of ATL, would then employ this ligand. Additionally, preliminary efforts toward bringing At-211 into clinical use have proven positive with the development of new linkers based upon trialkyl-stannyl chemistry for electrophilic displacement by At-211 and radiolabeling humanized anti-Tac treating At as a halogen."

“肿瘤相关的单克隆抗体（mAb）是 潜在的治疗剂作为细胞毒性剂的选择性载体 到恶性细胞。该假设在动物模型系统中进行了检验 mab针对与各种相关的抗原 恶性肿瘤。使用的细胞固定剂各种 放射性核素。结合到 分析了单克隆抗体并将其与 仅单克隆抗体，用I-131或 结合到毒素。选择用于研究的几种放射性核素 跨越可用的放射性核素特性范围 排放能量，半衰期和物理的影响 排放的特征。研究继续关注 扩大Y-90的临床使用并完成临床前的临床 使用α-粒子发射放射性核素BI-212的研究， BI-213和AT-211。 NIH正在进行的临床试验 采用第二代双功能螯合剂 1B4M-DTPA（又名MX-DTPA）用于隔离Y-90。最近的 螯合设计技术的结果揭示了一个体内 双功能的绝对配置的依赖性 螯合剂以优化射电 - 金属复合稳定性。由于 这些结果，当前涉及1111，兰烷基离子的所有努力， BI-212,213已转换为执行 CHX-A'DTPA。未来的临床试验，例如计划的 与MAB 7G7与人源化抗TAC结合使用 ATL的处理将使用该配体。此外， 将AT-211用于临床使用的初步努力已有 基于 AT-211的亲电位移的试验甲基化学 和放射性标记为卤素治疗的人性化抗TAC。”