Optimal elimination of leukemic T cells from human bone marrow with
T101-ricin A-chain immunotoxin
P Casellas, X Canat, AA Fauser, O Gros, G Laurent, P Poncelet and FK Jansen
In view of bone marrow purging before autologous transplantation in T cell
malignancies, an anti-human T cell immunotoxin (IT) has been 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 micrograms/mL in the
presence of 10 mmol/L NH4Cl. This treatment led to the reduction of more
than six orders of magnitude of T101-positive clonogenic leukemic cells,
with no harm to T101-negative cells. Moreover, we observed no toxicity of
IT to human hematopoietic stem cells (CFU-GEMMT) derived from bone marrow
of healthy volunteers. Thus, 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.
Volume 65,
Issue 2,
pp. 289-297,
02/01/1985
Copyright © 1985 by The American Society of Hematology