In vitro model of toxin therapy targeted against murine myeloid leukemia cells

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The current major obstacles in cancer chemotherapy include acquisition of multidrug resistance and resting cancer cells that are not in the cell cycle. In this paper we discuss one of the candidate strategies for overcoming these problems, focusing on the treatment of myeloid leukemias. A family of protein toxins is made by plants and bacteria, and these act within the cell cytoplasm to inhibit protein synthesis; Pseudomonas exotoxin (PE), diphtheria toxin (DT), and ricin are particularly well known. Toxins and conventional chemotherapeutic agents have different mechanisms of action. Therefore, cancer cells that are naturally resistant or acquire resistance to chemotherapeutic agents will not be cross-resistant to toxin-based therapies. Furthermore, toxins are potentially cytotoxic for nondividing cells that cannot be killed by conventional drugs. These unique properties make them attractive for use in the treatment of cancer. For this purpose, PE, DT, and ricin have been chemically or genetically attached to monoclonal antibodies and polypeptide hormones to direct their cytotoxic activities to specific eukaryotic cells [14, 15]. Pseudomonas exotoxin

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