Comparisons of the results of marrow grafts applied to the treatment of human acute myelogenous leukemia (AML) in first remission have repeatedly demonstrated that the incidence o leukemic relapse following a transplant from an allogeneic HLA-matched sibling is markedly lower than that following a transplant from a syngeneic twin. The nature of this allogeneic advantage is complex and likely reflects the summation of contributions from several different effector systems which destroy or inhibit the regrowth of residual leukemic cell populations in the host surviving the preparative cytoreduction administered prior to transplant. The contribution of allogeneic effector cells to the process of eradication of surviving leukemic cells is strongly supported by recent studies documenting the induction of both clinical and cytogenetic remissions in patients who have relapsed with CML (chronic myelogenous leukemia) or AML following an allogeneic transplant who have been treated with single or multiple infusions of peripheral blood leukocytes derived from the original marrow donor. In this project, we propose to develop a murine model for examining human donor effector cell interactions with human host leukemic cells so as to compare and characterize different lymphoid effector cells, including NK cells, LAK cells, and cytotoxic or cytoinhibitory T-lymphocytes specific for major or minor alloantigens or leukemia selective antigens for their capacity to alter the growth and dissemination of host leukemic cells in a xenografted murine model. Using this model, we also wish to determine whether and to what degree observed anti-leukemic activities can be augmented through the coadministration of biologicals, including recombinant cytokines and leukemia reactive monoclonal antibodies which can stimulate the cytolytic or cytoinhibitory activities of these effector cells or target these cells to sites of leukemia cell growth.
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