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  • 陈晓,周薇,王方策,等.DC-OVA疫苗在裸鼠体内的抗肿瘤效应[J].同济大学学报(医学版),2015,36(4):1-6.    [点击复制]
  • CHEN Xiao,ZHOU Wei,WANG Fang-ce,et al.Anti-tumor effect of DC-OVA vaccine in nude mice[J].同济大学学报(医学版),2015,36(4):1-6.   [点击复制]
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DC-OVA疫苗在裸鼠体内的抗肿瘤效应
陈晓,周薇,王方策,王龙,蒋涛,赵培林
0
(同济大学医学院组织学与胚胎学教研室,上海 200092)
摘要:
目的 构建靶向树突状细胞(dendritic cell, DC)的肿瘤疫苗DC-OVA系统,探讨DC-OVA肿瘤疫苗在祼鼠体内的抗肿瘤效应及相关机制。方法 构建表达肿瘤抗原OVA的树突状细胞。建立携带OVA的Lewis肺癌细胞(Lewis lung cancer cell-OVA, LLC-OVA)的皮下荷瘤裸鼠模型,瘤旁注射DC-OVA疫苗,通过记录肿瘤大小观察肿瘤生长抑制状况。以IHC方法观察肿瘤组织CD3、Nestin、CD133阳性细胞;观察脾DC相关分子(CD11c、OVA)的阳性表达以及T细胞(CD3+)的分布、数量和功能变化。同时,应用ELISA方法检测血清中IL-12的表达水平。结果 DC-OVA疫苗预防组与PBS对照组比较,呈现出明显的肿瘤生长抑制(P<0.05)。与对照组相比,DC-OVA疫苗治疗组肿瘤明显缩小(P<0.001)。疫苗治疗3次组与治疗1次组比较,效果更明显(P<0.05)。于实验第4周,疫苗治疗1次组与对照组比较,CD3阳性表达高,Nestin、CD133阳性表达低(P<0.05);治疗1次组血清IL-12含量较对照组升高(P<0.001);第8周,治疗1次组血清IL-12含量较第4周治疗组及第8周对照组低。结论 DC-OVA疫苗特异性杀伤了LLC-OVA肿瘤细胞,使肿瘤干细胞表达Nestin、CD133减少。
关键词:  树突状细胞  肺肿瘤细胞  DC疫苗  肿瘤免疫治疗  祼鼠
DOI:10.16118/j.1008-0392.2015.04.001
投稿时间:2015-01-22
基金项目:上海市教委科研创新重点项目(08ZZ19)
Anti-tumor effect of DC-OVA vaccine in nude mice
CHEN Xiao,ZHOU Wei,WANG Fang-ce,WANG Long,JIANG Tao,ZHAO Pei-lin
(Dept. of Histology & Embryology, Medical College, Tongji University, Shanghai 200092, China)
Abstract:
Objective To prepare DC-OVA vaccine system and to investigate its anti-tumor effect in Lewis lung cancer bearing nude mice. Methods Ovalalbumin(OVA) plasmid was transfected into dendritic cells(DC) to construct DC-OVA and cytotoxic T cells were activated by DC-OVA. The DC-OVA vaccine system was prepared. Lewis lung cancer cells+OVA were inoculated in nude mice, and the tumor-bearing(LLC-OVA) nude mice were treated with DC-OVA. The tumor growth was measured by vernier caliper; the expression of CD11c, OVA and CD3 in mice spleen, the expression of CD3, Nestin and CD133 in tumor tissue were detected by immunohistochemistry(IHC); serum IL-12 in nude mice was measured by ELISA. ResultsCompared with control group, vaccine prevention group presented significant inhibition effect on tumor growth(P<0.05). Compared with control group the tumor size was significantly smaller in vaccine treatment group(P<0.001). The tumor-inhibition effect in nude mice with 3-time treatment was more marked than that with one-time treatment(P<0.05). In week 4 compared with control group, the expression of CD3 in vaccine treatment group was higher and expression of Nestin and CD133 was lower(P<0.05). The serum IL-12 in vaccine treatment group was significantly increased(P<0.001) at week 4; however, serum IL-12 in treatment group at week 8 was lower than that in treatment group at week 4 and control group at week 8(both P<0.001). Conclusion DC-OVA vaccine system can prevent and treat tumor-bearing nude mice, and it is effective in inhibiting tumor stem cells expressing Nestin and CD133.
Key words:  dendritic cells  lung cancer cell  DC vaccine  tumor immunotherapy  nude mice

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