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An immunotoxin with therapeutic potential in T cell leukemia: WT1-ricin A.

Abstract
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.
AuthorsC D Myers, P E Thorpe, W C Ross, A J Cumber, F E Katz, W Tax, M F Greaves
JournalBlood (Blood) Vol. 63 Issue 5 Pg. 1178-85 (May 1984) ISSN: 0006-4971 [Print] United States
PMID6370334 (Publication Type: Journal Article)
Chemical References
  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Antitoxins
  • Membrane Glycoproteins
  • thymus-leukemia antigens
  • Ricin
Topics
  • Antibodies, Monoclonal (immunology, physiology)
  • Antigens, Neoplasm (immunology)
  • Antitoxins (pharmacology, therapeutic use)
  • Binding Sites, Antibody
  • Bone Marrow (drug effects, metabolism)
  • Bone Marrow Transplantation
  • Cell Line
  • Cell Transformation, Neoplastic (drug effects, pathology)
  • Cytotoxicity, Immunologic
  • Hematopoietic Stem Cells (drug effects, metabolism)
  • Humans
  • Immunotherapy
  • Leukemia, Lymphoid (drug therapy, immunology, pathology)
  • Membrane Glycoproteins
  • Ricin (metabolism, pharmacology, therapeutic use)
  • T-Lymphocytes (immunology)

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