KDR基因重组的T7噬菌体疫苗构建及其对小鼠Lewis肺癌抑制作用的研究  

Construction of KDR gene recombinant T7 phage vaccine and its inhibitory effect on Lewis lung cancer in mice

作　　者：孙红梅[1] 唐亮[2] 刘岽[2] 李晓慧[1] 周彩存[2] 谈立松[2] 王丽萍[1] 张培德[3] 张尚权[4] 

机构地区：[1]郑州大学医学院第一附属医院肿瘤科,郑州450052 [2]上海市肺科医院肺癌免疫研究室,上海200433 [3]复旦大学生命科学学院生物化学系,上海200433 [4]中国科学院上海生物化学与细胞生物学研究所,上海200031

出　　处：《肿瘤》2006年第11期970-974,共5页Tumor

基　　金：上海市科委重点课题项目(编号:03DZ19236)

摘　　要：目的：构建KDR基因重组的T7噬菌体疫苗以及探讨其对小鼠Lewis肺癌的抗肿瘤作用。方法：克隆KDR的膜外Ⅱ区基因,构建KDR基因重组T7噬菌体疫苗,免疫小鼠,免疫四次后接种Lewis肺癌,观察肿瘤的生长情况,14 d后脱颈椎杀死小鼠,眼球取血、取出瘤体称重,计算抑瘤率,观察抗肿瘤效果。ELISA检测小鼠血清抗KDR抗体滴度。结果：实验组抑制程度明显,肿瘤生长速度最慢,肿瘤重量与生理盐水组和空白噬菌体组相比有统计学差异(P＜0．05),抑瘤率可达57．0%,远大于空白噬菌体组(16．0%)。小鼠血清稀释至1∶500,小鼠特异性抗人源KDR抗体仍呈阳性。结论：KDR基因重组的T7噬菌体疫苗对小鼠Lewis肺癌具有明显的抗肿瘤作用,用人源KDR作为免疫原免疫小鼠通过免疫交叉反应可以打破对自身抗原的免疫耐受,产生特异性的免疫反应。Objective： To construct KDR gene recombinant T7 phage vaccine and investigate its anti-tumor effect on mice with Lewis lung cancer. Methods：The gene encoding the domain Ⅱ of the extracellular region of KDR was cloned into the T7 phage genome to construct phage vaccine. Then the vaccine was applied to immune mice. After the 4th immunization, Lewis lung cancer cells were inoculated. The weight of tumor was determined after 14 d to investigate the anti-tumor effect. The serum level of the specific antibody against human KDR was determined by ELISA. Results： The recombinant T7 phage was successfully constructed. The tumor growth in the experimental group was inhibited most obviously and the tumor weight in this group was significantly lower than that in both the normal saline group and phage control group （P〈0.05）. And its tumor inhibition rate was 57.0 %, which was significantly higher than the phage control group （16.0%）. Specific antibody against human KDR was still positive by ELISA when the mouse serum was diluted to 1/500. Conclusion： The KDR gene recombinant phage vaccine had obvious anti-tumor effect on mice with Lewis lung cancer. Homo sapiens KDR phage vaccine could break the immune tolerance of mice to self-antigen through cross-reaction and induce specific anti-tumor immunity.

关 键 词：肺肿瘤 血管内皮生长因子受体-2 噬菌体T7 癌症疫苗 

分 类 号：R73-3[医药卫生—肿瘤] R392.11[医药卫生—临床医学]