Monoclonal Antibodies to Target Neuronal Populations

描述（由申请人提供）：该提案涉及用单克隆抗体靶向体内特定神经元群体的试剂的开发。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转运蛋白的单克隆抗体。在这个II期申请中，第一个特定目标是创建针对另一类重要细胞表面分子的细胞外结构域的单克隆抗体，即G蛋白偶联受体。这些受体在人体健康的各个方面发挥着重要作用，反映了它们在人体生理学，特别是神经系统中的广泛存在。选择这五种生长抑素受体是因为它们在神经系统、生物学和神经系统病理学中的重要性。第二个具体目标是创建针对这些受体的重组抗体。这些抗体中最好的将被修饰，以证明生物活性分子可以插入表达生长抑素受体的细胞中。该提案有几个创新之处。开发用于植入生物活性细胞的试剂对于开发治疗神经退行性疾病和疼痛病理等疾病的新疗法非常重要。尽管重组抗体在癌症生物学中广泛使用，它们具有通过构建融合蛋白进行修饰的能力，但它们仍然非常罕见，这使得这成为一种新颖的方法。

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.