Press O W
Department of Medicine, University of Washington, Seattle.
Biotherapy. 1991;3(1):65-76. doi: 10.1007/BF02175100.
Immunotoxins (ITs) are chimeric molecules constructed by covalently conjugating monoclonal antibodies (MoAbs) to plant or bacterial toxins (e.g. ricin or pseudomonas exotoxin). The antibody moiety allows specific targeting of ITs to tumor-associated antigens, while the toxin moiety is responsible for cell killing by irreversible inactivation of protein synthesis. Since ITs must reach the cytosol to kill cells, the rates of endocytosis, the pathways of intracellular routing, and the rates of translocation to the cytoplasm are important determinants of the efficacy of an IT. Promising in vitro and in vivo IT results have been reported by many groups, and phase I clinical trials in cancer patients are currently underway.
免疫毒素(ITs)是通过将单克隆抗体(MoAbs)与植物或细菌毒素(如蓖麻毒素或铜绿假单胞菌外毒素)共价结合而构建的嵌合分子。抗体部分使免疫毒素能够特异性靶向肿瘤相关抗原,而毒素部分则通过不可逆地使蛋白质合成失活来负责细胞杀伤。由于免疫毒素必须到达细胞质溶胶才能杀死细胞,所以内吞速率、细胞内转运途径以及向细胞质的转运速率是免疫毒素疗效的重要决定因素。许多研究小组都报告了免疫毒素在体外和体内取得的有前景的结果,目前针对癌症患者的I期临床试验正在进行。