COMPARATIVE ANALYSIS OF IN VIVO T CELL DEPLETION WITH RADIOTHERAPY, COMBINATION CHEMOTHERAPY, AND THE MONOCLONAL ANTIBODY CAMPATH-1G, USING LIMITING DILUTION METHODOLOGY

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Abstract
We have investigated the efficacy of standard conditioning regimens for bone marrow transplantation in depleting functional T lymphocytes in vivo and have compared it with the efficacy of the monoclonal antibody Campath-1G. Using limiting dilution techniques the frequencies of proliferating T cell precursors (PTL), cytotoxic T cell precursors (CTL-p), helper T cell precursors (HTL-p), and mature helper T cells (HTL) were determined before and after treatment. Both total body irradiation and combination chemotherapy with busulfan/cyclophosphamide were highly efficient at depleting PTL, CTL-p, and HTL-p (0-4 days) but spared HTL to a variable extent (0-99.5%). In the majority of patients treated with Campath-1G a similar degree of PTL, CTL-p, and HTL-p depletion was achieved, and, in addition, HTL were effectively removed (> 95.5%). These results suggest that Campath-1G could be successfully employed in depleting radio- and chemotherapy-resistant host T lymphocytes prior to T-depleted bone marrow transplantation.