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.
|
Authors | C D Myers, P E Thorpe, W C Ross, A J Cumber, F E Katz, W Tax, M F Greaves |
Journal | Blood
(Blood)
Vol. 63
Issue 5
Pg. 1178-85
(May 1984)
ISSN: 0006-4971 [Print] United States |
PMID | 6370334
(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)
|