Chemical Modifications of Antibodies for Tumor Targeting

这个项目是由C.H. Paik博士开发和指导的，研究重点是通过化学修饰来提高单克隆抗体和片段的肿瘤靶向性。在2000财年，我们研究了一种新的多步骤肿瘤靶向治疗方法。我们的策略包括用单克隆抗体（MoAb）肽预先靶向肿瘤，然后注射放射性标记的第二肽。这种方法将抗体注射与放射标记注射分离，从而提供抗体与肿瘤抗原结合的特异性，同时消除放射标记的MoAb由于其大尺寸而导致血液清除缓慢的问题。该项目包括moab肽偶联物、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MoAb的免疫反应性的完整性，并允许肽的二聚化形成。我们用荷瘤裸鼠进行的初步多步骤肿瘤靶向实验显示，一种放射性标记肽在肿瘤组织中积累高，而在非肿瘤组织和血液中积累低，从而提供了高的肿瘤与本底放射性比。

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.