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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 Protein¹

University of Heidelberg, Heidelberg, West Germany [F.M.U.], and Department of Biochemistry, University of Kansas, Lawrence, Kansas 66045 [S.R., L.L.H.]

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.

¹ This work was supported in part by Grant CA 29889 from the National Cancer Institute.

² Present address: Department of Therapeutic Radiology, University of Minnesota, Minneapolis, MN 55455.

³ Present address: Cetus Corporation, 1400 Fifty-third Street, Emeryville, CA 94608.

Received 5/30/84. Accepted 9/21/84.

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