This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The elimination of leukemia following allogeneic hematopoietic cell transplantation (HCT) is in part attributable to an immune response termed the 'graft versus leukemia' (GVL) effect in which residual leukemia cells are thought to be destroyed by donor T cells reacting with recipient minor histocompatibility (H) antigens(1-7). In many patients who undergo allogeneic HCT, however, a GVL effect sufficient to eradicate the underlying leukemia fails to develop, and the transplant ultimately fails due to recurrence of the malignancy. Attempts to enhance the GVL effect through the adoptive transfer of unselected, polyclonal T lymphocytes from the donor have in general been unsuccessful because donor lymphocyte infusion (DLI) produces few, if any, durable antileukemic responses but causes much morbidity and mortality due to the development of graft-versus-host disease (GVHD)(8-11). This study addresses whether adoptive transfer of donor-derived CD8+ cytotoxic T lymphocyte (CTL) clones specific for minor histocompatibility (H) antigens of the recipient that are expressed in hematopoietic cells but have limited expression in non-hematopoietic cells can be a less toxic but more effective treatment for patients with recurrence of acute leukemia after allogeneic HCT.
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