We have been successful in our effort to create and characterize a panel of monoclonal antibodies and Ig related fusion proteins. Various different techniques, including cDNA immunization have been successfully used in Dr. Kuchroo'laboratory to make monoclonal antibodies to soluble and cell surface proteins. We have made antibodies to mouse, human, rat and hamster proteins. In addition, Dr. Zheng has successfully generated dozens of Ig-fusion proteins. To understand biological functions of a newly identified protein, Ig fusion proteins have been utilized for identifying in vitro and in vivo function of the molecules. In this effort cytokines or cell surface proteins have been fused with the heavy chain of IgG, and we have recently established a collaborative core between Xin Xiao Zheng, Vijay Kuchroo and Terry B. Strom to build a antibody and fusion protein Core within the Transplant Research Center at Beth Israel Deaconess Medical Center and Center for Neurologic Diseases, Brigham and Women's Hospital. Both Centers are located in the Harvard Institutes of Medicine. The investigators meet regularly for planned meeting for impromptu consultation. The investigators have a long history of working together and producing monoclonal antibodies and fusion proteins to a number of cell surface targets. The recent collaboration has led to the generation of monoclonal antibodies and Ig fusion proteins to TIM family of molecules, a family of newly discovered immunoregulatory molecules expressed on the surface of T cells. The antibodies against specific proteins can be generated that can act as an agonist and activate the receptor or an antagonist and block the function of the molecule. Ig fusion proteins, on the other hand, have an advantage of binding to the natural ligand and can be utilized as tools to identify and molecularly clone the ligand. Furthermore, Ig fusion proteins can act as blocking agents and interfere with the binding of receptor:ligand interaction and therefore help in the understanding the in vivo function of the molecule. Ig proteins also have long half-lives and minimal immunogenicity, therefore can be used successfully in vivo for understanding the function of the newly identified molecule. The antibodies and Ig 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, cancer and induce transplantation tolerance. The goals of antibody and fusion protein Core will be to provide a platform for developing monoclonal and polyclonal antibodies and novel therapeutic Ig.fusion proteins for newly discovered molecules or genes for PPG. Our role will be to provide antibodies and fusion proteins for newly identified proteins. While the 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 to a clinical trial in the future.
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