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. ? ?
