含多种免疫原的疫苗治疗大鼠脑胶质瘤  

Multiple antigen peptide vaccine against rat gliomas

作　　者：曾山 彭里磊 陆笑非 明扬 张苓 何海平 陈礼刚 

机构地区：[1]西南医科大学附属医院神经外科,四川泸州646000 [2]西南医科大学附属医院放射科,四川泸州646000

出　　处：《中华神经外科杂志》2017年第7期740-744,共5页Chinese Journal of Neurosurgery

基　　金：四川省科技厅重点科技自筹项目（2013SZZ002）;四川省科学技术厅一泸州市人民政府一泸州医学院联合科研专项资金（LZ-LY-9）;四川省卫生和计划生育委员会普及应用项目（16PJ557）

摘　　要：目的探讨同种异基因型的肿瘤细胞及其裂解物与同基因型的肿瘤细胞裂解物作为免疫原制成的混合疫苗对大鼠胶质瘤的治疗作用。方法以同种异基因型的c6细胞及其裂解物与同基因型的9L细胞裂解物作为免疫原制备混合疫苗，建立9L／Fisher344大鼠胶质瘤模型，并随机分为空白组、20万治疗组、30万治疗组，每组分别为10只大鼠。于术后第1天进行免疫治疗，观察荷瘤大鼠的生存期，术后第10、20、30、40、50天行MRI检查分析肿瘤的体积变化，同时于术后第20天行HE染色及免疫组化分析观察肿瘤的侵袭力变化。结果治疗组生存时间较空白组显著延长，差异有统计学意义（P〈0．05）；MRI增强扫描发现，空白组肿瘤呈现持续生长，而治疗组呈先增大后减小生长。方差分析各组接种第20天时肿瘤的体积，空白组肿瘤体积为（451．25±9．36）mm^3，大于20万治疗组[（122．52±22．30）mm^3）]和30万治疗组[（112．06±17．97）mm^3]，差异有统计学意义（P〈0．05）。HE染色发现治疗组肿瘤细胞密度稍低于空白组。免疫组化检测发现空白组Podoplanin及Fascin染色呈强阳性表达，明显高于治疗组，而两治疗组之间的差异无统计学意义（P〉0．05）。结论以同种异基因型的c6细胞及其裂解物与同基因型的9L细胞裂解物作为免疫原制备的混合疫苗能够显著延长荷瘤大鼠的生存期，并降低胶质瘤组织的侵袭力。Objective To investigate the therapeutic effect of mixed vaccines which consist allogeneic tumor cells as well as their lysates and syngenic cell lysates in the rat model of glioma. Methods Mixed vaccines were made which contained allogeneic C6 cells and their lysates and syngenic 9L cell lysates. The 9L/ Fisher 344 glioma model was established in rats which were randomly divided into blank group, 200,000 treatment group and 300,000 treatment group. Immunotherapy was initiated at the l th day after intracranial inoculation of 9 L cells. The survival time of rats was documented. The tumor volume was analyzed on MRI images at the I0 th, 20 th, 30 th, 40 th, 50 th day after 9L cells were injected into the brain, and HE staining and immunohistochemical analysis of invasion changes were conducted at the 20 th day post inoculation. Results The survival time in treatment groups was significantly longer than that in blank group （P 〈 0.05）. The enhanced MRI showed that the tumor in blank group continued to grow, while tumors in treatment groups grew during the initial phase and then decreased. Analysis of variance was conducted to assess the tumor volume at 20 th day. The tumor volume in blank group [ （451.25±9.36） mm3 ] was significantly greater than that in the 200,000 treatment group [ （ 122.52 ± 22.30） mm^3 ） 1 and 300,000 treatment group [ （ 112.06 ± 17.97） mm^3] （P 〈 0.05 ）, and there was no significant difference between those two treatment groups. The tumor cell density in treatment group was lower than that in blank group assessed by HE staining. In the blank group, more positive cells were found within tumor in both Fascin staining and Podoplanin staining compared with the two treatment groups, which had no significant difference （ P 〈 0. 05 ）. Conclusion Mixed vaccines that consist of allogeneic tumor ceils as well as their lysates and syngenic cell lysates might be useful in siznificant orolonzinz of the rat＇s survival time and reducinz the invasiveness of gliomas.

关 键 词：神经胶质瘤 免疫治疗 疫苗 大鼠 

分 类 号：R739.41[医药卫生—肿瘤]