IMMUNOTOXIN AND ONCOTOXIN THERAPY OF CANCER CELLS

假单胞菌外毒素(PE)或转基因形式的PE已被 附着在单抗或生长因子上以产生细胞- 特定的细胞毒剂。突变的PE分子I所在的结构域 用TGFAlpha、IL2、IL4、IL6、CD4或单链抗体组合取代 这些区域是通过基因融合产生的，嵌合蛋白产生于 大肠杆菌，并纯化到接近均一的水平。这样的分子可能在 消除肿瘤细胞或其他导致几个人 疾病。突变分析已经被用来描述 体育的各个领域。PE阻断基因第276位和279位的突变 细胞毒性可能是通过阻止PE的蛋白分解过程来实现的。突变 在PE的羧基末端通过干扰 一种加工形式的PE的移位。CD4-PE40的活性一直是 进一步的评估和嵌合毒素已被发现阻止传播 并对几种不同的HIV毒株具有活性 以及SIV。

Pseudomonas exotoxin (PE) or genetically modified forms of PE have been attached to monoclonal antibodies (mAbs) or growth factors to create cell- specific cytotoxic agents. Mutant PE molecules in which domain I has been replaced by TGFalpha, IL2, IL4, IL6, CD4 or single chain antibody combining regions have been created by gene fusion, the chimeric proteins produced in E. coli, and purified to near homogeneity. Such molecules may be useful in the elimination of tumor cells or other cells responsible for several human diseases. Mutational analysis has been used to delineate the function of the various domains of PE. Mutations at positions 276 and 279 of PE block cytotoxicity probably by preventing proteolytic processing of PE. Mutations at the carboxyl end of PE abolish cytotoxicity by interfering with translocation of a processed form of PE. The activity of CD4-PE40 has been further evaluated and the chimeric toxin has been found to block the spread of HIV in vitro and to be active against several different strains of HIV as well as SIV.