Anti-T cell monoclonal antibodies conjugated to ricin as potential reagents for human GVHD prophylaxis: effect on the generation of cytotoxic T cells in both peripheral blood and bone marrow.
Three murine anti-human monoclonal antibodies broadly reactive with human T cells were conjugated to intact ricin toxin. The purgative effects of these immunotoxins (IT) on alloreactive T cells after in vitro pretreatment was tested in an in vitro assay measuring the generation of cytotoxic T cells (CTL). Pretreatment was performed in the presence of lactose to block the native binding of ricin, thus rendering IT antibody specific. Blocking studies with free antibody showed that selective toxicity was determined by the antibody moiety of the antibody-toxin conjugate. Our assay system permitted the measurement of significant CTL levels in the bone marrow. Thus, we were able to determine the differential selectivity of IT for T cells as compared with stem cells in the same donor preparation. Our studies show that antibody-intact ricin conjugates have great potential as T cell purgative reagents for GVHD prophylaxis in human BMT.
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000502:physiology*; D001667:Binding, Competitive; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D003602:Cytotoxicity, Immunologic; D006086:Graft vs Host Disease / Q000276:immunology / Q000628:therapy*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D012276:Ricin / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D012276:Ricin