T-cell depletion with ricin A-chain T101 in allogeneic bone marrow transplantation to prevent severe graft-versus-host disease

Abstract

Bone marrow cells from 10 marrow transplant donors were treated with an immunotoxin, which couples A-chain of ricin with a monoclonal anti-T-cell antibody T101 to prevent graft-versus-host disease by the elimination of mature T-cells. Marrow cells treated with the anti human T-cell immunotoxin (IT101) were cultured for erythropoietic colonies, granulocytic colonies, and multilineage hematopoietic colonies (CFU-GEMMT) containing myeloid cells and T-cells, and optimal conditions were defined for the elimination of T-cells present in the harvested donor marrow prior to marrow transplantation. Marrow samples purged with IT101 were examined for residual T-cells by fluorescence activated cell sorting, using anti-T-cell antibodies, [3H]-thymidine incorporation after PHA stimulation, and an assay for clonogenic T-cells. The number of T-cell colonies observed in the treated marrows was less than 5% of the number in comparable unpurged donor marrows. Treatment with IT101 did not alter the plating efficiency of hematopoietic colonies compared to untreated donor marrow cells. These data suggest that multilineage progenitors responsible for the reconstitution of the recipient hematopoietic system are not affected by marrow IT101 purging. The clinical data on 10 patients indicate that the depletion of T-cells in the donor marrow with IT101 is effective in decreasing the severity of acute graft-versus-host disease in allogeneic marrow transplantation and warrants continued investigation.