Studies on the ability of monoclonal antibodies to selectively mediate complement-dependent cytotoxicity of human myelogenous leukemia blast cells.
A panel of monoclonal antibodies that bind to leukemic blast cells from patients with acute myelocytic leukemia and chronic myelocytic leukemia in blast crisis was studied for their ability to mediate complement-dependent lysis of a variety of cell populations from patients with leukemia, normal blood cells, and human leukemia cell lines. Several of these monoclonal antibodies were selectively cytotoxic to myeloid leukemia cells (AML-1-99, AML-1-211, AML-2-30, CML-75, CML-115, and CML-150). Although they were all capable of binding to normal cell populations, none of these hybridomas were cytotoxic to normal cells. Three of these antibodies (AML-1-211. CML-75, and CML-150) were cytotoxic to some leukemia cell samples only after dilution of the hybridoma supernatant, i.e., they showed a prozone. Binding of these three antibodies, as well as another, AML-1-201, as determined in a radioimmunoassay, also showed a prozone. Other monoclonal antibodies are described (AML-2-23 and AML-2-9) that mediate complement-dependent cytotoxicity to myeloid leukemia cells as well as selected normal cell types (monocytes and lymphocytes, respectively). The potential clinical utility of these monoclonal antibodies is considered in the context of recently encountered problems in the use of monoclonal antibodies to mediate leukemia cell lysis in vivo.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003165:Complement System Proteins / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D003165:Complement System Proteins