Preliminary clinical study of transferrin-adriamycin conjugate for drug delivery to acute leukemia patients.

Molecular biotherapy Pub Date : 1990-03-01
W P Faulk, C G Taylor, C J Yeh, J A McIntyre
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Abstract

Seven patients with acute leukemia were treated intravenously with low doses of transferrin-Adriamycin conjugate. The total amount of drug given each patient was far below known toxicity levels for free Adriamycin. The number of tumor cells in peripheral blood diminished in treated patients, and bone marrow aspirates showed no evidence of disease progression. Two patients gave a febrile response and no hypersensitivity reactions were observed. Results of parallel basic research have shown that transferrin receptors on acute leukemia cells bind transferrin-Adriamycin conjugates, and kill by mechanisms at either the plasma membrane or nuclear levels, or both. Such conjugates may provide an alternative to monoclonal antibody drug targeting.

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转铁蛋白-阿霉素偶联物给药急性白血病的初步临床研究。
采用低剂量转铁蛋白-阿霉素偶联物静脉治疗7例急性白血病患者。给每个病人的药物总量远远低于已知的游离阿霉素的毒性水平。接受治疗的患者外周血中肿瘤细胞的数量减少,骨髓抽吸没有显示疾病进展的证据。2例患者出现发热反应,无超敏反应。平行基础研究结果表明,急性白血病细胞上的转铁蛋白受体结合转铁蛋白-阿霉素偶联物,并通过质膜或核水平或两者的机制杀死细胞。这种偶联物可以提供单克隆抗体药物靶向的替代方法。
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