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鉴于白血病细胞异常高地表达IL-6/IL-6R系统,而正常造血细胞几乎不表达抑或微量表达这一事实,我们本研究率先在国际上开展了利用IL-6/IL-6R系统介导重组IL-6-PE40外毒素融合蛋白特异性杀伤高表IL-6R白血病新策略的科学性及可行性的探讨.构建并表达及纯化IL-6-PE40;应用核酸及蛋白质序列软件GOLDKEY系统计算机模拟分析IL-6-Linker-PE40及IL-6-PE40的柔性、抗原性、亲水性及表位等分子生物学特性;建立了表达人IL-6R的大鼠急性早幼粒白血病细胞模型;鉴定了人IL-6R基因在LT12中的表达;分析了人IL-6R基因的整合对LT12-IL-6R~+细胞模型生物学特征的影响及IL-6-PE40对白血病及正常造血细胞的体外作用和IL-6R的白血病及正常大鼠的体内效应.结果发现:①利用
In view of the fact that leukemia cells express IL-6 / IL-6R system abnormally high, whereas normal hematopoietic cells express little or no expression, we first took an international initiative to mediate the recombination using IL-6 / IL-6R system IL-6-PE40 exotoxin fusion protein specific killing high table IL-6R leukemia new strategy of scientific and feasibility of construction and expression and purification of IL-6-PE40; using nucleic acid and protein sequence software GOLDKEY system computer simulation The molecular biological characteristics such as flexibility, antigenicity, hydrophilicity and epitope of IL-6-Linker-PE40 and IL-6-PE40 were analyzed. A rat acute promyelocytic leukemia cell model expressing human IL- The effect of IL-6R gene integration on the biological characteristics of LT12-IL-6R ~ + cell model was analyzed and the effect of IL-6-PE40 on leukemia and normal hematopoietic cells In vitro effects and IL-6R leukemia and normal rats in vivo results showed that: ① use of