Faulk W P, Taylor C G, Yeh C J, McIntyre J A
Center for Reproduction and Transplantation Immunology, Methodist Hospital of Indiana, Indianapolis 46202.
Mol Biother. 1990 Mar;2(1):57-60.
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.
七名急性白血病患者接受了低剂量转铁蛋白-阿霉素偶联物的静脉注射治疗。每位患者所给予的药物总量远低于游离阿霉素已知的毒性水平。接受治疗的患者外周血中的肿瘤细胞数量减少,骨髓穿刺检查未显示疾病进展的迹象。两名患者出现发热反应,未观察到超敏反应。平行的基础研究结果表明,急性白血病细胞上的转铁蛋白受体与转铁蛋白-阿霉素偶联物结合,并通过质膜或核水平或两者的机制杀死细胞。此类偶联物可能为单克隆抗体药物靶向治疗提供一种替代方法。