Antibodies against specific proteins can be generated as an agonist to activate the receptor or an antagonist to block the function of the molecule. Similarly, an Fc fusion protein consisting of the ectodomain of a given protein can serve as blocking reagent to disrupt signaling events downstream of its ligand. By contrast, a fusion protein consisting of the ligand for a receptor of interest will function to stimulate receptor-mediated signaling. Both antibodies and Fc fusion proteins are unique reagents and have been proven to be a powerful tools to facilitate innovative research in many fields and some have proven to be potent immunomodulatory reagents to treat human autoimmune diseases and cancers. We have well-established platforms for both antibody and Fc fusion protein generation, production, purification, quality control, and functional characterization. We have been successful in our effort to create and characterize a panel of monoclonal antibodies and Fc fusion proteins. The antibodies that we have made include anti-mouse and human CTLA-4, CD94, CD226, TIGIT, Tim-2, Tim-3 and Tim-4, and the Fc fusion proteins that we have made include CTLA4/Fc, PD-1/Fc, Tim-1/Fc, Tim-3/Fc, Tim-4/Fc. Some of these antibodies have been made, purified, and provided to PPG investigators for their work. In addition to these antibodies, we have generated a panel of rear earth metal-labelled monclonal antibodies for use in CyTOF, with qualified CyTOF staining protocols. These reagents facilitated innovative research by PPG investigators and led to a series of important publications. The panel of well qualified custom made antibodies, fusion proteins and CyTOF reagents will ensure progress of each of the research projects. Based on the well established techniques for monoclonal antibody and Fc fusion protein generation in Dr. Kuchroo's lab, we aim to established an antibody and fusion protein core at Ann Rommey Center for Neurologic Diseases, Brigham and Women's Hospital to facilitate antibody generation and production for the needs of this PPG. The core leader has an excellent record working on therapeutic antibody and Fc fusion protein generation, assay development, production and purfication with 25 years of experience. He has been working on generation of monoclonal antibodies and fusion proteins to a number of cell surface targets. His recent efforts has led to the generation of monoclonal antibodies to mouse and human Tim proteins and other immunoregulatory molecules including TIGIT expressed on the surface of T cells. The goal of this antibody and fusion protein core is to generate novel monoclonal antibodies and Fc fusion proteins for this PPG. We will also collaborate with PPG project leaders for antibody screenings and characterizations. In addition, the core will produce and purify the antibodies that were previously generated by PPG investigators for the needs of the proposed studies. While the antibodies and Fc fusion proteins produced by the core will not be manufactured in a GMP facility, the cell lines used for production will meet FDA standards. Thus it will be possible to easily progress for use in clinic in the future.
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