Elimination of human leukemia by monoclonal antibodies in an athymic nude mouse leukemia model.
A human acute myeloid leukemia model has been developed by i.v. transplantation of HL-60 myeloid leukemia cells into Swiss nude mice pretreated with cyclophosphamide. HL-60 cells disseminated into hematopoietic tissues as determined by flow cytometric analysis, fluorescence microscopy, fluorescence in situ hybridization analysis, and colony formation assay. Passive immunotherapy using murine anti-CD13 (F23) or anti-CD33 (M195) mAbs was able to eliminate completely the HL-60 cells in the mice, as determined by fluorescence in situ hybridization analysis, colony formation assay, and culture of mouse blood and tissue cells in vitro. Although F23 is able to inhibit completely CD13/aminopeptidase N enzymatic activity, actinonin, another potent inhibitor of CD13/aminopeptidase N, was not active as an antileukemic agent. HL-60 cell surface antigens, including CD13 (aminopeptidase N) and CD33 (p67), down-regulated over time, and murine anti-HL-60 antibody was generated while the cells grew in the mice. This response was suppressed by cyclophosphamide. These data suggest that leukemia cell elimination was antibody mediated.
Xu
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Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Scheinberg
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DA
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000032:analysis; D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis / Q000276:immunology; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D015415:Biomarkers / Q000032:analysis; D018826:CD13 Antigens / Q000032:analysis / Q000276:immunology; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D018922:HL-60 Cells / Q000276:immunology / Q000637:transplantation; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007167:Immunotherapy; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D063268:Sialic Acid Binding Ig-like Lectin 3; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018906:Antineoplastic Agents, Alkylating; D015415:Biomarkers; C571163:CD33 protein, human; C571165:Cd33 protein, mouse; D007074:Immunoglobulin G; D063268:Sialic Acid Binding Ig-like Lectin 3; D003520:Cyclophosphamide; D018826:CD13 Antigens