The purpose of these studies is to examine the proliferative and cytotoxic immune responses that can be demonstrated by culturing human lymphocytes with HLA matched and mismatched leukemia cells and other abnormal histocompatible cells in vitro. This will be done using the mixed lymphocyte culture (MLC), primed lymphocyte typing (PLT), and cell-mediated lysis (CML) assays with primary, secondary, and cloned T-cell responses. Leukemic blasts will be obtained from patients by bone marrow aspiration at diagnosis and at relapse. Cryopreserved blasts will be used as stimulating and target cells in MLC and CML assays. Responding cells in these cultures will be autologous remission lymphocytes or lymphocytes from HLA identical or haplo-identical relatives. To facilitate studying antileukemic responses, we will address methodological problems and immunologic specificity utilizing model systems in which helper and cytotoxic responses are stimulated by autologous lymphocytes that have been labeled with bacterial antigen or transformed by the Epstein-Barr virus. Our objectives are to: (1) examine the induction requirements, antigenic specificity, and HLA restriction of human lymphocytes primed in vitro to abnormal histocompatible tissues; (2) evaluate the potential relationship between this in vitro response in the clinical course of leukemic patients, especially those who have just received bone marrow transplants, with emphasis on factors that may influence the ability to generate an """"""""antileukemic"""""""" immune response; and (3) generate large numbers of polyclonal and single cell-derived populations of leukemia reactive T cells by in vitro expansion with interleukin 2 containing T-cell growth factor in order to further examine the specificity of these cells and generate the in vitro data required to initiate clinical trials of adoptive cellular immunotherapy in appropriately selected high-risk patients with leukemia and other neoplasms. (LB)
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