This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Graft-versus-leukemia (GVL) effect contributes to the efficacy of Hematopoietic stem cell transplantation (HSCT), but is associated with graft-versus-host disease (GVHD). One goal of current HSCT research is to maximize the GVL effect while minimizing the chances of significant GVHD. This might be accomplished by infusing T cells that preferentially recognize and lyse leukemic host cells as compared to normal non-malignant host tissues. Two proteins - WT1 and Proteinase 3 (PR3, or Myeloblastin) - are overexpressed in leukemic cells and been associated with poorer prognosis in AML, ALL and CML patients. WT1 and PR3 is also necessary for the survival of the leukemic cell. CD8+ T-cell clones have been generated that recognise and lyse leukemia cells that overexpress WT1 and PR3. This is a Phase I/II trial that examines the safety and potential efficacy of infusing CD8+ T cell clones specific for WT1 in patients with Leukemia and Myelodysplastic syndrome (MDS) that has relapsed after HSCT (or prophylactically in patient at highest risk). Patients who are at high risk for relapse and are undergoing HLA-matched allogeneic HSCT at the Fred Hutchinson Cancer Research Center for Acute Myeloblastic Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), MDS and Chronic Myeloid Leukemia (CML) are eligible. Donor derived CD8+ cells are stimulated with autologous peptide-loaded antigen specific cells, followed by cloning, expansion and cryopreservation in a GMP facility. When treatment is indicated, the clones are expanded and infused in a dose-escalating manner (5 infusions). Last two doses are followed by 2 weeks of low dose IL-2.
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