One of the most promising clinical applications for monoclonal antibodies is in the selective and complete removal of malignant cells from human bone marrow prior to autologous transplantation. To measure elimination of tumor cells a clonogenic assay has been developed that utilizes Burkitt's lymphoma tumor cell lines which bear one or more of a group of markers including the common acute lymphoblastic leukemia antigen (CALLA), gp 26, Bl, Ia, HLA, B2 microglobulin and certain T cell differentiation antigens. One or more monoclonal antibodies are available which react with each of these markers. Using this model, requirements for the elimination of malignant cells from human bone marrow can be explored systematically. We will determine whether susceptibility of different tumor cell lines can be correlated with antigen binding, antigenic modulation, complement activation, complement binding, osmotic fragility or membrane repair. Resistant clones can be isolated, permitting analysis of mechanisms by which tumor cells avoid antibody mediated cytotoxicity. Understanding mechanisms of resistance may permit a more rational approach to the elimination of malignant cells from human bone marrow. Treatment of bone marrow with antibodies against differentiation antigens such as CALLA or gp 26 removes subpopulations of normal cells as well as tumor cells. Techniques have been developed for the isolation of CALLA+ and gp26+ precursors from fetal liver and bone marrow. Monoclonal reagents will be used as probes to define the role of these differentiation antigens in normal lymphoid development and function.
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