OPTIMAL ELIMINATION OF LEUKEMIC T-CELLS FROM HUMAN-BONE MARROW WITH T101-RICIN A-CHAIN IMMUNOTOXIN

Abstract

In view of bone marrow purging before autologous transplantation in T cell malignancies, an anti-human T cell immunotoxin (IT) was prepared by coupling ricin A-chain to the monoclonal antibody T101 that binds the T1 differentiation antigen expressed by T lymphocytes as well as by T cell-derived hematologic malignancies. Using a sensitive and reliable clonogenic assay, optimal conditions were defined for the elimination of clonogenic human T leukemic cells among bone marrow cells. Maximal cytoreduction was obtained with IT at a dose of 2 .mu.g/ml in the presence of 10 mmol/l NH4Cl. The treatment led to the reduction of more than 6 orders of magnitude of T101-positive clonogenic leukemic cells, with no harm to T101-negative cells. No toxicity of IT to human hematopoietic stem cells (CFU-GEMMT) derived from bone marrow of healthy volunteers was observed. Pretreatment of bone marrow samples with IT plus NH4Cl offers a safe, simple, reliable, and highly efficient means to eliminate undesirable leukemic T cells from the graft.