重组腺病毒鼠CD40L对小鼠淋巴瘤治疗和预防作用的体内研究  

Recombinant adenovirus encoding mCD40L gene therapy improves therapeutic efficacy of murine lymphoma

作　　者：李红[1] 赵丽娜[1] 白力允[2] 郭秀臣[1] 刘爱春[1] 

机构地区：[1]哈尔滨医科大学附属第三医院血液淋巴内科,黑龙江哈尔滨150081 [2]新乡医学院第三附属医院肿瘤内科,河南新乡453003

出　　处：《现代肿瘤医学》2013年第5期960-964,共5页Journal of Modern Oncology

基　　金：黑龙江省自然科学基金资助项目(编号:D200939);哈尔滨市科技创新人才研究专项资金项目(编号:2009RFLXS005)

摘　　要：目的:探讨重组腺病毒鼠CD40-ligand基因(Adv-mCD40L)对小鼠淋巴瘤的免疫治疗作用及免疫预防作用。方法:构建含有小鼠CD40L基因的重组腺病毒载体,体外转染小鼠B淋巴瘤细胞(A20细胞)。流式细胞术检测A20细胞转染前后表面CD80、CD86、CD40L(CD154)、CD40表达情况。在体内实验中,治疗组首先建立小鼠A20荷瘤模型,分别于肿瘤内多点注射Adv-mCD40L和Adv;预防组小鼠预先分别接种负载A20细胞抗原的Adv-mCD40L和Adv,免疫后再次接种具有活性的A20细胞,均以生理盐水作为对照,观察小鼠成瘤时间及肿瘤生长情况。结果:体外转染mCD40L基因24h内CD154和CD40表达水平改变,48h后A20表达CD80、CD86增强。经Adv-mCD40L免疫后的小鼠成瘤时间较其他组明显延迟。经mCD40L基因治疗的小鼠均可见瘤体生长速度明显受抑,肿瘤大小分别与经Adv及NS治疗的小鼠比较,有显著差异(P<0.05)。结论:转染mCD40L基因可以增强A20表面协同刺激分子的表达,增强A20细胞的免疫原性,激活机体的抗肿瘤免疫,延缓成瘤时间,抑制肿瘤生长。Objective：To investigate the therapeutic effect of recombinant adenovirus encoding mouse CD40 -ligangd gene（ Adv - mCD40L） on treatment for mice with lymphoma and the protective effect of Adv - mCD4L vaccine loaded with mouse A20 lymphoma cells on the tumor - beating BALB/c mice. Methods： mCD40L gene was transfected into mouse A20 cells mediated by recombinant adenovirus in vitro, the expression levels of costimulatory molecules CD80, CD86, CD154 and CD4 phenotype of A20/mCD40L cells were assessed using flow cytometry. A mouse tumor model was set up by s. c. inoculation of 1 × 10^6/mouse A20 tumor cells. Adv - mCD40L and Adv were injected,and a new tumor occurred in the mice, the tumor size was observed. The immunized mice with Adv - mCD40L vaccine loaded with mouse A20 lymphoma cells were injected with A20 tumor cells, and observed whether a new tumor occurred in the mice. Results： The expression levels of CD80 and CD86 were higher in A20/mCD40L cells than those on parent cells. The tumor of mice immunized with Adv - mCD40L vaccines showed new tumor occurred later than the mouse injected with Adv and the controls. The tumor of mice injected with Adv - mCD4L vaccines grew slower than that injected with Adv and controls. The tumor size was smaller than those treated with Adv and NS, statistically showed significantly different. Conclusion ： The transfeetion of mCD40L into mouse A20 cells can enhance the expression levels of eostimulatory molecules, delay occurrence of new tumor,inhibit growth of tumor.

关 键 词：CD40L配体 重组腺病毒载体 肿瘤免疫 淋巴瘤 

分 类 号：R733[医药卫生—肿瘤]