Comparative analysis of in vivo T cell depletion with radiotherapy, combination chemotherapy, and the monoclonal antibody Campath-1G, using limiting dilution methodology.
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 (greater than 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.
Theobald
M
M
Department of Internal Medicine III, Ulm University Hospital, West Germany.
Hoffmann
T
T
Bunjes
D
D
Heit
W
W
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002066:Busulfan / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D006648:Histocompatibility; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007958:Leukocyte Count / Q000187:drug effects / Q000528:radiation effects; D008208:Lymphatic System / Q000528:radiation effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D014916:Whole-Body Irradiation
D000911:Antibodies, Monoclonal; D003520:Cyclophosphamide; D002066:Busulfan