CELL THERAPY

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Core C: Cell Therapy. This is a new core that will take advantage of new physical space resources to consolidate efforts relating to cell therapies developed and applied in this program. This core will therefore provide four specific functions: (1) specimen procurement, prioritization, and distribution for research, in coordination with the Clinical Cytotherapy/Transplant Laboratory, inpatient units, and outpatient clinics, and including a centralized storage repository (all Projects 1-6); (2) graft characterization by flow cytometry, clonogenic assays, and lymphocyte functional assays to develop predictors of graft outcome (Project 6); (3) production and release of NK cells and antigen (CMV and WT-1)-specific T cells for adoptive immunptherapy, including the generation of human dendritic cells and EBV-transformed B cell lines for lymphocyte stimulation and expansion ex vivo (Projects 1, 4, and 6); and (4) coordinated QA/QC oversight of these activities (Project 6). The actual cell processing for hematopoietic stem cell transplantation will remain with the Clinical Cytotherapy Laboratory. Additionally, the activities conducted by the Clinical Cytotherapy Laboratory are largely billable as clinical patient care and do not require support from this core. This core will also interact with Core B by providing the upfront graft characterization that will help interpret posttransplant monitoring of myeloid (including dendritic cell) and lymphoid reconstitution pertinent to graft outcome. The integration of these previously separate efforts will provide greater efficiency of effort and costs, will enhance patient care by improved characterization of allograft biology, and will provide NK and Ag-specific T cell therapies to address major early complications of disease recurrence and opportunistic infections. Lay summary and public health relevance: Fewer complications and the availability of alternative donors to matched siblings have made allogeneic hematopoietic stem cell transplantation available to larger numbers of patients. These include older patients and those with coexisting medical problems. Laboratory support provided by this Core will sustain research and development in this area as well as translational applications in the proposed clinical trials. These activities will help improve the overall outcomes of patients undergoing allogeneic transplant each year for an increasing variety of malignancies.