Chemical Modifications of Antibodies for Tumor Targeting

该项目由C.H.Paik，Ph.D.负责开发和指导。这项研究的重点是通过化学修饰提高单抗和片段的肿瘤靶向性。在2000财年，我们研究了一种新的多步肿瘤靶向的使用。我们的策略包括用单抗(MOAB)多肽预先靶向肿瘤，然后注射放射性标记的第二多肽。这种方法将抗体注射从放射性标记注射中分离出来，从而提供了抗体与肿瘤抗原结合的特异性，同时消除了与放射性标记单抗由于其大小而导致的血液清除缓慢相关的问题。该项目涉及合成Moab-多肽结合物、清洗剂和放射性标记多肽。我们一直在优化这些试剂的合成，以保持摩押免疫反应性的完整性，并允许多肽的二聚化形成。我们使用荷瘤裸鼠进行的初步多步肿瘤靶向实验显示，放射性标记的多肽在肿瘤组织中高度积聚，在非肿瘤组织和血液中低积聚，从而提供高肿瘤与本底的放射性比率。

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.