Monoclonal Antibodies to Target Neuronal Populations

描述（由申请方提供）：本提案涉及开发用单克隆抗体体内靶向特定神经元群体的试剂。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克隆抗体。在该II期申请中，第一个具体目标提出创建针对另一类重要的细胞表面分子（G蛋白偶联受体）的胞外结构域的单克隆抗体。这些受体在人类健康的各个方面发挥着重要作用，反映了它们在人类生理学，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。第二个具体目标提出创建针对这些受体的重组抗体。最好的这些抗体将被修改，以证明生物活性分子可以插入到表达生长抑素受体的细胞。该提案的创新之处有几个。用于插入生物活性细胞的试剂的开发对于开发用于神经退行性疾病和疼痛病理学等的新疗法将是重要的。尽管在癌症生物学中广泛使用重组抗体，其能够通过构建融合蛋白进行修饰，但它们仍然非常罕见，使其成为一种新方法。

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.