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Abstract: Graft-versus-host disease (GVHD) is a frequent major complication of allogeneic hematopoietic cell transplantation (HCT). Approaches that selectively deplete T cells that cause GVHD from allogeneic stem cell grafts and preserve T cells specific for pathogens may improve HCT outcomes. It has been hypothesized that the majority of T cells that can cause GVHD reside within the naïve T cell (TN) subset, and previous studies performed in mouse models and with human cells in vitro support this hypothesis. As a prelude to translating these findings to the clinic, we developed and evaluated a novel 2-step clinically compliant procedure for manipulating peripheral blood stem cells (PBSC) to remove TN, preserve CD34+ hematopoietic stem cells, and provide for a fixed dose of memory T cells (TM) that includes T cells with specificity for common opportunistic pathogens encountered after HCT. Our studies demonstrate effective and reproducible performance of the immunomagnetic cell selection procedure for depleting TN. Moreover, after cell processing, the CD45RA-depleted PBSC products are enriched for CD4+ and CD8+ TM with a central memory phenotype and contain TM cells that are capable of proliferating and producing effector cytokines in response to opportunistic pathogens. [Copyright &y& Elsevier]

Abstract: Animal models and human studies of allogeneic hematopoietic cell transplantation (HCT) demonstrate that immunologic nonidentity between donor and recipient is responsible for a graft versus leukemia (GVL) effect that contributes to complete tumor eradication. A variety of immune cells have been implicated in the GVL effect including NK cells, B cells, and CD4+ and CD8+ T cells that recognize minor histocompatibility (H) or leukemia-associated antigens. Here we discuss strategies for employing T cells specific for minor H antigens to augment the GVL effect. [Copyright &y& Elsevier]