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 long-term objective of these proposed studies is to improve leukemia treatment using targeted adoptive immunotherapy. Hematopoietic stem cell transplantation (HSCT) has been a powerful tool in the treatment of leukemia, often providing the chance for cure when chemotherapy alone is insufficient. A vital element contributing to the efficacy of HSCT is the graft-versus-leukemia (GVL) effect, as evidenced by the anti-tumor activity of both donor lymphocyte infusions (DLI) in the treatment of relapsed chronic myeloid leukemia (CML) post-HSCT and nonmyeloablative HSCT. An unfortunate side effect in these settings, however, is the high rate of associated acute and chronic graft-versus-host disease (GVHD) resulting in significant morbidity and mortality. Thus, one goal of current HSCT research is to maximize the GVL effect while minimizing the chances of significant GVHD. The work being proposed includes Phase I/II studies that will examine the safety and potential efficacy of infusing CD8+ T cell clones specific for WT1 in patients with leukemia that has relapsed after HSCT, who have been selected for the trial based on the poor prognosis of such patients and lack of effective treatment options. The methods currently being used to generate T cells for these clinical trials are based on similar adoptive immunotherapy trials underway in our program targeting other antigens and diseases. A major objective of these preliminary Phase I clinical trials is to estimate the toxicity rate associated with infusing donor CD8+ CTL clones specific for WT1 in patients at high risk for posttransplant relapse of leukemias.
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