In vivo biotherapy of HL-60 myeloid leukemia with a genetically engineered recombinant fusion toxin directed against the human granulocyte macrophage colony-stimulating factor receptor
| Autor: | Jp, Perentesis, Gunther R, Waurzyniak B, Yanishevski Y, Myers DE, Ek O, Messinger Y, Shao Y, Lm, Chelstrom, Schneider E, We, Evans, Fatih M. Uckun |
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| Rok vydání: | 1998 |
| Předmět: |
Immunotoxins
Recombinant Fusion Proteins Transplantation Heterologous Cytarabine HL-60 Cells Mice SCID Disease-Free Survival Macaca fascicularis Mice Leukemia Promyelocytic Acute Doxorubicin Receptors Granulocyte-Macrophage Colony-Stimulating Factor Animals Humans Diphtheria Toxin Female Tissue Distribution |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1078-0432 |
| Popis: | Acute myeloid leukemia (AML) is the most common form of acute leukemia. Contemporary chemotherapy regimens fail to cure most patients with AML. We have genetically engineered a recombinant diphtheria toxin human granulocyte macrophage colony-stimulating factor (GMCSF) chimeric fusion protein (DTctGMCSF) that specifically targets the GMCSF receptor on fresh human AML cells and myeloid leukemia cell lines. At a nontoxic dose level, DTctGMCSF therapy was superior to the standard chemotherapeutic agents 1-beta-D-arabinofuranosylcytosine and Adriamycin, resulting in 60% long-term event-free survival of severe combined immunodeficient mice challenged with an otherwise invariably fatal cell dose of the human HL-60 myeloid leukemia. Notably, systemic exposure levels of DTctGMCSF, which were found to be therapeutic in the severe combined immunodeficient mouse xenograft model of human HL-60 myeloid leukemia, could be achieved in cynomolgus monkeys without any significant nonhematological toxicities. The recombinant DTctGMCSF fusion toxin might be useful in the treatment of AML patients whose leukemias have recurred and developed resistance to contemporary chemotherapy programs. |
| Databáze: | OpenAIRE |
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