hMIP-1β基因修饰瘤苗体内诱导抗肿瘤免疫效应的研究  

Antitumor effects induced by hMIP-1β gene modified tumor vaccine in vivo

作　　者：罗小玲[1] 谢裕安[1] 匡志鹏[1] 吴继宁[1] 梁安民[1] 

机构地区：[1]广西医科大学附属肿瘤医院实验研究部,广西南宁530021

出　　处：《中华肿瘤防治杂志》2008年第5期335-338,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：广西科技厅青年基金资助项目(桂科青0447049)

摘　　要：目的:探讨人巨噬细胞炎性蛋白-1β(hMIP-1β)基因修饰瘤苗体内诱导的抗肿瘤免疫效应。方法:通过重组腺病毒载体介导将hMIP-1β基因导入CT26细胞中,X-gal染色法检测基因转染效率;ELISA法检测hMIP-1β基因修饰CT26细胞培养上清中hMIP-1β的含量;Boyden趋化小室法检测培养上清对CD4+T细胞、CD8+T细胞、NK细胞及未成熟树突状细胞(imDCs)的趋化作用;制备hMIP-1β基因修饰的CT26细胞瘤苗并免疫BALB/c小鼠,观察其诱导免疫细胞的杀伤活性和保护性免疫反应。结果:腺病毒载体可介导hMIP-1β基因转染CT26细胞和表达(X-gal染色的阳性率>95%),培养上清中hMIP-1β水平为980pg/mL,并对CD4+T细胞、CD8+T细胞、NK细胞及im-DCs有显著的趋化作用,与转染对照基因LacZ的CT26细胞及野生型CT26细胞比较差异均有统计学意义,P<0.01。hMIP-1β基因修饰的CT26细胞瘤苗免疫小鼠能有效诱导肿瘤特异性CTL活性和非特异性NK活性,产生明显的免疫保护作用,可抵抗肿瘤细胞的再攻击,成瘤率降低,肿瘤生长速度减慢,小鼠生存期延长。结论:hMIP-1β基因修饰瘤苗可诱导产生有效的抗肿瘤免疫保护作用,有希望成为预防肿瘤转移与复发的有效手段。OBJECTIVE：To investigate antitumor effects induced by hMIP-1β gene modified tumor vaccine in vivo. METHODS： Murine colorectal adenocarcinoma CT26 cells were transfected with a recombinant adenovirus carring the hMIP-1β gene （AdhMIP-1β）, then the gene transfected efficiency was tested by the X-gal method. The hMIP-1β level in supernatants of hMIP-1β gene-modified CT26 cells was assayed by ELISA, and the chemotactic activities for CD4^＋ T cells, CD8^＋ T cells, NK cells and immature dendritic cells （imDCs） were assayed by a transwell chamber. The BALB/c mice were immunized with hMIP-1β gene-modifled CT26 tumor vaccine and the antitumor effects were investigated. RESULTS： hMIP-1β gene was transfected into CT26 cells by AdhMIP-1β with efficiency more than 95 %. The level of hMIP-1β in the culture supernatant of hMIP-1β gene-modlfied CT26 cells was 980 pg/mL and the supernatant displayed significant chemotactic activities to CD4＋ T cells, CD8＋ T cells, NK cells and im- DCs compared with LacZ gene-modified CT26 cells and the control group, P〈0.01. The mice immunized with hMIP-1β gene-modified CT26 tumor vaccine induced tumor special CTL activities and non-special NK activities, and exhibited resistance to later challenge with wild-type CT26 cells, and the percentage of the mice with detectable tumor decreased and the survival time of tumorbearing mice prolonged. CONCLUSIONS： hMIP-1β gene-modified tumor vaccine could induce a powerful protective antitumor im- mune response. The data suggests that hMIP-1β gene-modified tumor vaccine should play a potent role in preventing the metastasis and recurrence of malignant tumor.

关 键 词：肿瘤/免疫学 癌症疫苗 基因 AdhMIP-1β 肿瘤 实验性/免疫学 

分 类 号：R730.5[医药卫生—肿瘤]