| Abstract: |
Combination chemotherapy produces remissions in patients with acute myeloid leukemia (AML). However, the majority of patients ultimately relapse and die with cytotoxic drug resistant blasts. Novel agents which circumvent resistance are needed. One such class are AML-cell surface targeted proteins. These genetically engineered polypeptides are hybrid molecules composed of two moieties-a haptophore which triggers AML cell binding and a toxophore which kills the cell. The haptophore or ligand portion consists of a monoclonal antibody or antibody fragment or a cytokine. These peptides react with cell surface receptors or antigens on AML cells. The haptophore is genetically or chemically linked to the toxophore. The toxophore may consist of an antibody Fc domain which triggers antibody-dependent cell cytotoxicity, a DNA-damaging cytotoxic drug, a radionuclide or a protein synthesis-inactivating peptide toxin. The toxophore may provide a cell death signal that overcomes standard resistance phenotypes. Further, the targeting provided by the haptophore may reduce normal tissue toxicities. This review describes some of the properties of the cell surface molecular targets, the reactive haptophores and toxophores and how these functional peptides have been optimally combined to kill leukemic blasts in patients with AML. |
| Keywords: |
unclassified drug; acute granulocytic leukemia; busulfan; clinical trial; review; cytotoxic agent; cancer combination chemotherapy; antineoplastic agents; methotrexate; protein domain; animals; mice; cell death; lung toxicity; protein targeting; cyclophosphamide; cytokine; antibodies, monoclonal; anti-bacterial agents; antigen; immunoglobulin g; iodine 131; iodine radioisotopes; cardiotoxicity; leukemia, myeloid; ligand; remission; ligands; fc receptor; antigens, cd; corticosteroid; radioimmunotherapy; cell adhesion; cyclosporin; clinical trials; cell killing; acute disease; antigens, surface; gemtuzumab ozogamicin; antibody dependent cellular cytotoxicity; cell surface protein; immunoglobulin m; cell surface receptor; antigens, differentiation, myelomonocytic; blast cell; antigens, cd45; aminoglycosides; immunotoxins; monoclonal antibody m 195; hybridomas; toxin; tumor stem cells; monoclonal antibody cd33; monoclonal antibody cd45; antibody-dependent cell cytotoxicity; humans; human; priority journal; murine monoclonal antibody
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