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许多生物体可产生毒性物质,这些物质作用于哺乳动物细胞可引起从代谢异常到迅速杀死细胞等一系列有害变化。特别是假单胞菌外毒素(PE)、白喉毒素(DT)及蓖麻毒素(ricin)这类蛋白毒素,属于最有效的细胞杀伤剂,只要一个毒素分子进入癌细胞的胞浆中,就足以杀死细胞,故可用于治疗癌症。为达到治疗目的,须把这些毒素导向癌细胞表面的特定位置,使其内陷入细胞,最终进入细胞浆。此过程通过排除与毒素受体的结合,将毒素的杀细胞活性重新导向癌细胞上的受体或抗原,从而杀死癌细胞。通常将毒素与细胞结合蛋白如单克隆抗体或生长因子偶合,形成的结合物可选择性结合并杀死癌细胞,正常细胞因不能与这
Many organisms produce toxic substances that act on mammalian cells and cause a range of detrimental changes, from metabolic abnormalities to rapid killing of cells. In particular, protein toxins such as Pseudomonas exotoxin (PE), diphtheria toxin (DT) and ricin are the most effective cytotoxic agents. As long as one toxin enters the cytoplasm of cancer cells, Sufficient to kill cells, it can be used to treat cancer. For therapeutic purposes, these toxins must be directed to specific locations on the surface of the cancer cells, causing them to sink into the cell and eventually into the cytoplasm. This process kills the cancer cells by excluding the binding to the toxin receptor, redirecting the cytotoxic activity of the toxin to the receptors or antigens on the cancer cells. The toxins are usually coupled to a cell-binding protein, such as a monoclonal antibody or growth factor, and the resulting conjugate selectively binds and kills the cancer cells. Normal cells can not