Pre-clinical feasibility studies are presented to define a clinical system that selectively removes alloreactive T lymphocytes from allografts. The goal of these studies is the development a simple and automated process to generate therapeutic T cell products to support non-myeloablative stem cell transplantation by minimizing GVHD while providing immune competence to other antigens. A commercial system based on this concept will have significant value in making allo stem cell transplants more widely available. Currently, methods of T cell depletion or inactivation can control GVHD but result in infections, graft rejection and higher relapse rate. Recipient dendritic cells (DCs) generated from monocytes will be used to stimulate expression of CD25 on the alloreactive T cells. Recipient monocytes will be enriched by T and B lymphocyte depletion using the automated Isolex magnetic cell separator. An optimized protocol for generating dendritic in closed gas permeable containers will be developed. The Isolex will be used again to deplete CD25+ cells providing a cell product depleted of cells causing GVHD but replete with lymphocytes that protect against infection. Phase II studies will test these cells in a clinical trial and develop an automated system to make this procedure user friendly and applicable to routine practice.
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