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腺病毒介导的肝癌靶向SEA-CD80基因治疗及免疫学机制的初步研究
引用本文:司少艳,胡沛臻,黄杨,李侠,葛伟,张秀敏,隋延仿,张建中,张铭. 腺病毒介导的肝癌靶向SEA-CD80基因治疗及免疫学机制的初步研究[J]. 细胞与分子免疫学杂志, 2008, 24(3): 278-281
作者姓名:司少艳  胡沛臻  黄杨  李侠  葛伟  张秀敏  隋延仿  张建中  张铭
作者单位:1. 解放军第306医院中心实验室,北京,100101
2. 第四军医大学病理学教研室,陕西,西安,710032
基金项目:国家自然科学基金 , 军队医药卫生科研项目
摘    要:目的: 观察肝癌靶向性葡萄球菌肠毒素A (SEA)/CD80基因重组腺病毒载体对肝癌的疗效,并对其免疫学机制进行初步研究.方法: 利用AdEasy腺病毒系统分别构建并制备甲胎蛋白(AFP)启动子和增强子Ⅰ调控的SEA和/或CD80基因重组腺病毒载体, 然后采用瘤体内直接注射的方式对小鼠皮下移植性肝癌进行治疗, 采用RT-PCR和Western blot方法检测腺病毒注射部位的SEA和CD80 mRNA和蛋白的表达情况; 采用ELISpot方法和LDH释放实验分别检测脾脏淋巴细胞中肝癌特异性IFN-γ分泌细胞的频数和细胞毒性T细胞(CTLs)对Hepa1-6细胞的特异杀伤活性; 通过观察荷瘤小鼠经治疗后肿瘤体积的变化及生存时间, 评价重组腺病毒对肝癌的治疗作用.结果: 我们构建的腺病毒能够使SEA和/或CD80 mRNA和蛋白靶向地在肝癌组织中表达; 与空载体组和PBS对照组相比, 双基因组和单基因组分泌IFN-γ的T细胞数量均明显增多, CTL对Hepa1-6细胞的特异性杀伤作用均明显增强, 荷瘤小鼠肿瘤体积明显减小, 生存期明显延长; 双基因组的疗效和对免疫系统的激活作用明显高于单基因组; CD80 和SEA的组之间、空载体和PBS组之间无明显差异.结论: 我们制备的肝癌靶向性重组腺病毒对肝癌有良好的治疗作用, 联合基因治疗优于单个基因治疗.

关 键 词:葡萄球菌肠毒素A  CD80  共表达  腺病毒  肝癌  靶向治疗  病毒  肝癌组织  靶向  基因治疗  免疫学  机制  研究  mechanisms  immune  primary  hepatoma  Staphylococcal enterotoxin A  genetherapy  mediated  差异  激活作用  免疫系统  延长  生存期  增强
文章编号:1007-8738(2008)03-0278-05
修稿时间:2007-10-26

Adenovirus mediated targeted genetherapy of Staphylococcal enterotoxin A and CD80 for hepatoma and its primary immune mechanisms
SI Shao-yan,HU Pei-zhen,HUANG Yang,LI Xia,GE Wei,ZHANG Xiu-min,SUI Yan-fang,ZHANG Jian-zhong,ZHANG Ming. Adenovirus mediated targeted genetherapy of Staphylococcal enterotoxin A and CD80 for hepatoma and its primary immune mechanisms[J]. Chinese journal of cellular and molecular immunology, 2008, 24(3): 278-281
Authors:SI Shao-yan  HU Pei-zhen  HUANG Yang  LI Xia  GE Wei  ZHANG Xiu-min  SUI Yan-fang  ZHANG Jian-zhong  ZHANG Ming
Affiliation:Experimental Center for Medicine, 306th Hospital of PLA, Beijing 100101, China.
Abstract:AIM: To observe the effects of hepatoma-targeting recombinant adenovirus vectors of staphylococcal enterotoxin A (SEA) and/or CD80 gene on hepatoma and to study its immunological mechanisms. METHODS: Using AdEasy adenovirus system, we constructed recombinant adenovirus vectors of SEA and/or CD80 gene driven by alpha-fetoprotein (AFP) enhancer I and promoter. After intratumoral therapy for the mice bearing subcutaneous xenograft hepatoma with the recombinant adenoviruses, SEA and/or CD80 mRNA and protein were detected by RT-PCR and Western blot. IFN-gamma-producing cell frequency and specific cytotoxicity of T lymphocytes to Hepa1-6 cells were detected by ELISpot and LDH-released assay in the splenocytes. Effects of recombinant adenoviruses on hepatoma were assessed by changes of tumor volumes and survival time in the treated mice. RESULTS:The recombinant adenoviruses constructed by us made SEA and/or CD80 mRNA and protein targetedly express in hepatoma tissues. When compared with the empty vector and PBS groups, the IFN-gamma-producing cell frequency and specific cytotoxicity of T lymphocytes increased, the tumor volumes of mice decreased and the survival time increased in the double-gene and single-gene groups. Double genes elicited better antitumor effects and stronger immune responses. There were no significant differences in the effects between CD80 group and SEA group or between empty vector group and PBS group. CONCLUSION: The hepatoma-targeting recombinant adenovirus vectors constructed in this study can elicit effective antitumor effects on hepatoma and the effects of double genes are better than that of single gene.
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