转铁蛋白介导的单克隆抗体治疗胶质瘤动物模型

Fv fragment of the anti-transferrin receptor single chain antibody mediated therapeutic effect of survivin-siRNA on intracranial glioma in orthotopic mouse model

目的观察转铁蛋白受体单链抗体Fv片段介导的Survivin-siRNA治疗胶质瘤动物模型的效果。方法构建雌性裸鼠的胶质瘤动物模型,设计Survivin-siRNA,构建Survivin-siRNA质粒,构建单链Fv片段抗体-转铁蛋白,将单链抗体-转铁蛋白(scFV)与Survivin-siRNA结合。实验分为对照组、单纯质粒组、对照基因质粒组(Si-M组),Survivin-siRNA质粒组(SiS组),单链抗体Fv片段-转铁蛋白组(scFV组),转铁蛋白受体单链抗体Fv片段Survivin-siRNA组(Si-S-P-scFv组)。分别观察各组裸鼠脑内Survivin蛋白表达与各组裸鼠生存时间。结果小鼠Survivin蛋白表达,Si-S组受到轻度抑制,Si-S-P-scFv组受抑制较强(P<0.01)。小鼠生存时间,Si-S组高于对照组(P=0.02);与对照组和Si-S组比较,Si-SP-scFv组小鼠生存时间最长(分别为P<0.001,P=0.018)。结论转铁蛋白受体单链抗体Fv片段介导的Survivin-siRNA可较理想通过胶质瘤动物模型的血-脑脊液屏障,能明显延长实验动物生存时间。

Objective To observe the Fv fragment of the anti-transferrin receptor single chain antibody mediated therapeutic effect of survivin-siRNA on intracranial glioma in orthotopic mouse model. Methods The female nude mouse model of intracranial glioma was established. Survivin-siRNA was designed. The siRNA plasmid and the plasmids expressing the anti-transferrin receptor single chain Fv antibody were constructed. The siRNA and the antibody mentioned above were connected. The study was divided into 6 groups： control group, vector group, Si-M group, Si-S group, scFV group and Si-S-P-scFv group. The expression of Survivin and the survival time of the nude mice in each group were observed. Results The expression of survivin was slightly inhibited in Si-S group,but seriously inhibited in Si-S-P-scFv group（P〈0.01）. The survival time of the nude mice in Si-S group was longer than that in control group（P = 0.02）. Compared to control group and Si-S group, the survival time in Si-S-P-scFv group was longest（respectively P〈0.001, P = 0.018）. Conclusions The survivin-siRNA can be effectively delivered across the BBB to the brain in the mouse model of glioma mediated by the Fv fragment of anti-transferrin receptor single chain antibody and significantly prolong the survival time of the mice.