Multivalent Antibody Ligands for Clearance of Pathogens

描述(由申请人提供)： 这个项目的目标是设计、合成和测试多价配体同时与红细胞和血液传播病原体结合的要求，并通过将它们引导到肝脏来清除后者的循环。该配体将由开环复分解聚合(ROMP)衍生的带有抗体片段(Fab‘)官能化的嵌段共聚物组成。一半的聚合物将包含针对红细胞表面补体受体1型(CR1)受体的Fab‘，而另一半将使用针对金黄色葡萄球菌的Fab’进行功能化。这个项目是基于这样的知识，即针对CR1和其他细胞表面抗原的随机交联抗体复合体能够聚集这两种类型的细胞，并将非红细胞输送到肝脏中被摧毁。所提出的多价配体通过使用结构同质性，与以前实现类似目标的尝试相比提供了显着的改进。如果成功，该项目的结果将是一种快速和全面消除循环中病原体的有力方法。

DESCRIPTION (provided by applicant): The goal of this project is to design, synthesize, and test the requirements for a multivalent ligand to bind simultaneously to erythrocytes and blood borne pathogens and clear the latter from circulation by directing them to the liver. The ligand will be comprised of a ring opening metathesis polymerization (ROMP)-derived block copolymer functionalized with antibody fragments (Fab'). Half of the polymer will contain Fab' targeted against complement receptor type 1 (CR1) receptors on the surface of erythrocytes, while the other half will be functionalized with Fab' against Staphylococcus aureus. This project is based on the knowledge that randomly cross-linked antibody complexes specific for both CR1 and surface antigens on other cells are able to aggregate the two cell types and deliver the nonerythrocyte to be destroyed in the liver. The multivalent ligand proposed offers significant improvement over previous attempts towards similar goals through the use of structural homogeneity. If successful, the result of this project will be a powerful method for the rapid and general removal of pathogens from circulation.