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

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (1) , 69-75
Abstract
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 < 50% of pluripotent stem cells were lost. 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.