Monoclonal Antibodies to Target Neuronal Populations

描述(由申请人提供)：这项建议涉及到用单抗在体内靶向特定神经元群体的试剂的发展。这些试剂将用于研究和治疗应用。在第一阶段，我们开发了一种能够靶向神经元转运蛋白的单抗。在这个第二阶段的应用中，第一个特定的目标是创建针对另一类重要的细胞表面分子--G蛋白偶联受体的胞外区域的单抗。这些受体在人类健康的各个方面都发挥着重要的作用，反映了它们在人体生理，特别是神经系统中的广泛存在。这五种生长抑素受体之所以被选中，是因为它们在神经系统、生物学和神经系统病理学中具有重要意义。第二个具体目标是创造针对这些受体的重组抗体。这些抗体中最好的将被改造，以证明生物活性分子可以被插入到表达生长抑素受体的细胞中。该提案有几个创新之处。用于插入生物活性细胞的试剂的开发将对开发神经退行性疾病和疼痛病理等新的治疗方法具有重要意义。尽管重组抗体能够通过构建融合蛋白进行修饰，在癌症生物学中得到了广泛的应用，但它们仍然非常罕见，使其成为一种新的方法。

DESCRIPTION (provided by applicant): This proposal concerns the development of reagents to target specific neuronal populations in vivo with monoclonal antibodies. These reagents will be used in research and therapeutic applications. In Phase I, we developed a monoclonal antibody capable of targeting neuronal transporters. In this Phase II application, the first specific aim proposes to create monoclonal antibodies to the extracellular domains of another important class of cell surface molecules, the G protein-coupled receptors. These receptors play a large role in all aspects of human health, reflecting their widespread presence in the human physiology, especially the nervous systems. The five somatostatin receptors have been selected because of their importance in neuronal systems, biology, and nervous system pathologies. The second specific aim proposes to create recombinant antibodies to these receptors. The best of these antibodies will be modified to demonstrate that biologically active molecules can be inserted into cells that express the somatostatin receptors. The innovations in the proposal are several. The development of reagents for insertion of biologically active cells will be important for developing new treatments for neurodegenerative diseases and pain pathologies, among others. Despite widespread use of recombinant antibodies in cancer biology with their ability to be modified through the construction of fusion proteins, they are still extremely rare and make this a novel approach.