: The availability of novel cytokines, combined with the recent identification of functionally distinct leukocyte lineages and their progenitors, have created new opportunities for hematopoietic reconstitution and immune modulation, and provide the underlying rationale for this program project application. The proposed program brings together the collective expertise and experience of investigators who have developed techniques for isolating, growing and activating rare types of mononuclear leukocytes, and demonstrated their therapeutic effects in model systems. The objective of our program is to utilize these discoveries to develop more effective immune cell based therapies for disorders ranging from malignancies to autoimmune diseases. Three projects are described. Two of these projects seek to exploit the immunotherapeutic potential of dendritic cells loaded with tumor antigens. One focuses on a treatment for malignant lymphoma, a tumor of hematopoietic origin, while the other is focused on colorectal carcinoma, a solid tumor. In the third project, purified progenitor cells will be used to reconstitute the T cells of animals given lethal total body irradiation and allogeneic bone marrow transplants. These projects will be supported by four cores that provide essential services and reagents, including a flow cytometry core, another core that provides dendritic cell derived, antigen loaded exosomes and a final core that uses a recently developed system based on image analysis for monitoring cell trafficking in intact living animals. We believe that this interdisciplinary and interactive program will lead to the development of new and efficacious transfusion therapies for a variety of life threatening disorders.
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