Immunotoxin-mediated elimination of clonogenic tumor cells in the presence of human bone marrow.
An immunotoxin was synthesized with pokeweed antiviral protein and an IgG1 monoclonal antibody directed against human B and pre-B cells. The B43 murine monoclonal antibody does not react with normal human bone marrow precursor cells. The immunotoxin bound to all Burkitt's lymphoma cell lines that were tested but not to human peripheral blood T cells. The ability of antibody-toxin conjugate to inhibit human lymphoblast cell lines was checked in a clonogenic assay system. The immunotoxin in the presence of chloroquine elicited 5.8 logs of killing of Burkitt's lymphoma cells (B-ALL). The efficient inhibition of clonogenic growth of B-ALL cells was not affected by the presence of normal bone marrow cells. The immunotoxin was not very toxic to pluripotent stem cells; less than 50% of the stem cells were lost under conditions where 5.6 logs of clonogenic lymphoma cells were eliminated from a 100-fold excess of normal marrow cells. Further, when assayed by long-term human bone marrow cultures, immunotoxin treatment did not result in a significant loss of pluripotent precursor cells.
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D001666:Binding Sites, Antibody; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002051:Burkitt Lymphoma / Q000378:metabolism / Q000628:therapy; D002452:Cell Count; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D002999:Clone Cells / Q000276:immunology / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007945:Leukemia, Lymphoid / Q000378:metabolism / Q000628:therapy; D051379:Mice; D009699:N-Glycosyl Hydrolases; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D010940:Plant Proteins / Q000378:metabolism / Q000494:pharmacology*; D014176:Protein Biosynthesis; D054789:Ribosome Inactivating Proteins, Type 1; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D002738:Chloroquine; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein