Increased efficiency in selective elimination of leukemia cells by a combination of a stable derivative of cyclophosphamide and a human B-cell-specific immunotoxin containing pokeweed antiviral protein.
Leukemia cells were mixed with normal human bone marrow cells to simulate bone marrow from leukemia patients; the mixture was then treated with a combination of stabilized derivative of cyclophosphamide [Mafosfamide (ASTA Z 7557)] and pokeweed antiviral protein-containing immunotoxin. The ability of this protocol for selective elimination of B-ALL cells was evaluated by clonogenic assay. The monoclonal antibody (B43) portion of the immunotoxin was directed against human B-cells and was linked to pokeweed antiviral protein by a disulfide bond. The combination of ASTA Z 7557 and immunotoxin was superior to either ASTA Z 7557 or the immunotoxin alone and produced nearly 7 logs of elimination of leukemia cells from the cell mixtures. About 5 logs of contaminating tumor cells were eliminated from a 200-fold excess of normal marrow under conditions where fewer than 50% of pluripotent stem cells were lost. Moreover, this manipulation did not inhibit subsequent production of pluripotent stem cells in long-term bone marrow cultures, indicating that the more primitive progenitors were not harmed.
D000911:Antibodies, Monoclonal / Q000633:toxicity*; D000998:Antiviral Agents / Q000633:toxicity*; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000633:toxicity; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D007945:Leukemia, Lymphoid / Q000473:pathology*; D008223:Lymphoma / Q000473:pathology; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000633:toxicity*; D054789:Ribosome Inactivating Proteins, Type 1; D014410:Tumor Stem Cell Assay
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D002738:Chloroquine; C037933:Asta Z 7557; D003520:Cyclophosphamide; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein