Core E: Cell Processing and Storage will support this grant proposal by providing four specific functions. First, this core will provide critical instrumentation and technical expertise in cell procurement and processing of all clinical components necessary to support the treatment of patients with malignant diseases described in Projects 1-6. Direct funding is not requested for most of that activity, which is generally reimbursed by third party payers, but Core E will also procure and distribute research specimens and provide additional summary data to investigators. Second, the Core will characterize the bone marrow and PBSC components utilized in these allogeneic transplantation studies by quantitative flow cytometry for various T-cell and other lymphoid subsets. These data will be useful in determining which specific cell lineages may be correlated with clinical outcomes, which will in turn help to stimulate the development of novel graft engineering approaches and techniques that could improve future allogeneic transplantation studies. Third, Core E will operate a Repository of Research Specimens. This Repository will consist of two distinct types of components: (1) aliquots of patient and normal donor blood and/or bone marrow samples; (2) DNA preparations and established B-LCL lines obtained from allogeneic transplant patients and their corresponding normal donors. These samples will be critical in helping to define the mechanisms involved in engraftment, rejection, anti-tumor response and disease control, immune reconstitution, and the development of graft-versus-host disease. Material from this Repository will support studies outlined in Projects 1 , 2, 5, and 6. Fourth, Core E will be responsible for the development and clinical implementation of cell processing techniques necessary for the cGMP production of the WT1 and PR3 T-cells described in Project 5, and for the depletion of naive T-cells and subsequent generation of primed donor dendritic-cells described in Project 6. Integration of the clinical cell processing services of Core E with the projects contained within this grant application provides for better patient care, a higher degree of QA/QC, and significantly reduced efforts and costs. Relevance to public health: The support of Core E is critical to the success of the work proposed in the individual projects of this grant. This work promises to advance the field of allogeneic hematopoietic transplantation, making it safer, more effective, increasingly available and more appropriately applied. Such an advance could have obvious relevance to the thousands of patients who are transplanted each year or are potential candidates for transplantation.
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