人源化免疫毒素的研究进展

Humanized immunotoxins:research advances

免疫毒素是通过化学连接或基因融合的方法将细胞选择性配体与毒素分子相连组成的嵌合体蛋白,它能够靶向肿瘤细胞高表达的肿瘤相关抗原、膜受体和糖蛋白。尽管以细菌毒素或植物毒素为基础的免疫毒素显示出良好的应用前景,但细菌毒素和植物毒素的免疫原性和非特异的细胞毒性等因素,阻碍了它们在临床上的应用。针对这些问题,以人源蛋白如促凋亡蛋白与RNA酶为毒素部分的新一代免疫毒素被研发出来,本文对此类人源化免疫毒素的体内外实验研究进展进行综述。

Immunotoxins are chimeric proteins formed by a cell-selective ligand chemically hnkmg wltn or genetically fusing to a toxin moiety, and can target tumor-associated antigens, membrane receptors, or carbohydrate antigens overexpressing in cancer cells. In spite the application of bacterial and plant toxin based chimeric proteins is promising, clinical application is hampered by several factors like immunogenicity of the toxin moiety and nonspecific toxicity. In order to overcome these problems, a novel generation of immunotoxins, in which the cytotoxie moiety is an endogenous protein of human origin such as proapoptotic protein or RNase, have been developed. This review summarizes the advances of the new class of fusion protein in vivo and in vitro experimental study.