Chemical Modifications of Antibodies for Tumor Targeting

肿瘤靶向抗体的化学修饰

• 批准号: 6431804
• 负责人: JORGE A. CARRASQUILLO
• 金额: --
• 依托单位: CLINICAL CENTER
• 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/6431804
• 关键词: ABO(H) blood groups; acylating agent; autoradiography; blood /lymphatic neoplasm; blood banks; blood group incompatibility; blood transfusion; chemical elimination; clearance rate; erythrocyte count; erythrocytes; human subject; kidney metabolism; laboratory mouse; monoclonal antibody; neoplasm /cancer radionuclide diagnosis; nuclear medicine; physical chemical interaction; radionuclide diagnosis; radionuclides; radiopharmacology; rapid diagnosis; technetium

This project was developed and is directed by C.H. Paik, Ph.D. The research has centered on improving the tumor-targeting property of monoclonal antibodies and the fragments by chemical modifications. For FY 2000 we have investigated the use of a novel multistep tumor targeting. Our strategy involves pretargeting tumors with monoclonal antibody (MoAb) peptide followed by the injection of a radiolabeled second peptide. This approach decouples the antibody injection from the radiolabel injection, thereby offering the specificity of antibody binding to tumor antigens while eliminating problems associated with slow blood clearance of radiolabeled MoAb due to its large size. This project involves the synthesis of MoAb-peptide conjugates, clearing agents, and radiolabeled peptides. We have been optimizing the synthesis of these reagents to maintain the integrity of the immunoreactivity of MoAb and allow dimerization formation of peptides. Our preliminary multistep tumor-targeting experiments using tumor-bearing nude mice showed high accumulation of a radiolabeled peptide in tumor tissues and low accumulation in non-tumor tissues and blood, thereby providing high tumor-to-background radioactivity ratios.

该项目由C.H. Paik博士通过化学修饰提高单克隆抗体及其片段的肿瘤靶向性是目前研究的热点。在2000财政年度，我们研究了一种新的多步骤肿瘤靶向的使用。我们的策略包括用单克隆抗体（MoAb）肽预靶向肿瘤，然后注射放射性标记的第二种肽。这种方法将抗体注射与放射性标记注射分开，从而提供抗体与肿瘤抗原结合的特异性，同时消除了与放射性标记的MoAb由于其大尺寸而导致的缓慢血液清除相关的问题。该项目涉及MoAb-肽缀合物、清除剂和放射性标记肽的合成。我们一直在优化这些试剂的合成，以保持单克隆抗体的免疫反应性的完整性，并允许肽的二聚化形成。我们使用荷瘤裸鼠的初步多步肿瘤靶向实验显示放射性标记肽在肿瘤组织中的高积累和在非肿瘤组织和血液中的低积累，从而提供高的肿瘤与背景放射性比率。