An immunotoxin with therapeutic potential in T cell leukemia: WT1-ricin A
CD Myers, PE Thorpe, WC Ross, AJ Cumber, FE Katz, W Tax and MF Greaves
A conjugate of the monoclonal antibody WT1 and ricin A-chain was studied
for its suitability for purging marrow of leukemic T cells for autologous
transplantation in T cell acute lymphocytic leukemia (T- ALL). The
conjugate was powerfully cytotoxic to the human T-ALL cell line, GH1, which
expresses the WT1 antigen at a high density. Treatment of the cells with
the conjugate at 10(-11) M reduced their rate of protein synthesis by 50%,
and the inclusion of 6 mM ammonium chloride in the cultures enhanced the
potency of cytotoxic effect by 10-100- fold. Clonogenic assays indicated
that less than 0.1% of GH1 cells survived 3-hr exposure to the conjugate in
ammonium chloride. WT1 alone did not react with multipotent (CFU-GEMM)
hematopoietic progenitors in normal human bone marrow, as measured by
fluorescence-activated cell sorting. Under conditions giving maximal
killing of GH1 cells, there was no toxicity to multipotential progenitors
in normal human marrow.
Volume 63,
Issue 5,
pp. 1178-1185,
05/01/1984
Copyright © 1984 by The American Society of Hematology
