Plasmid DNA encoding human carcinoembryonic antigen (CEA) adsorbed onto cationic microparticles induces protective immunity against colon cancer in CEA-transgenic mice.

Plasmid DNA encoding human carcinoembryonic antigen (CEA) adsorbed onto cationic microparticles induces protective immunity against colon cancer in CEA-transgenic mice.
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吸附在阳离子微粒上的编码人癌胚抗原(CEA)的质粒DNA可在CEA转基因小鼠中诱导针对结肠癌的保护性免疫。

DOI:
10.1016/s0264-410x(02)00821-6
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发表时间:
2003
期刊:
影响因子:
5.5
通讯作者:
Xiang,Rong
Xiang,Rong
中科院分区:
医学3区
文献类型:
--
作者:
Luo,Yunping;O'Hagan,Derek;Zhou,He;Singh,Manmohan;Ulmer,Jeffrey;Reisfeld,RalphA;JamesPrimus,F;Xiang,Rong

文献摘要

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一种基于癌胚抗原(CEA)的DNA疫苗,吸附在聚(dl-乳酸-羟基乙酸酯)(PLG)的阳离子微颗粒上,在CEA转基因小鼠中诱导对MC38-CEA结肠癌细胞的致命攻击的肿瘤保护免疫,其效果比相应的裸DNA疫苗更有效。用编码小鼠GM-CSF的质粒增强疫苗的效力,使50%的小鼠完全排斥肿瘤细胞。这种作用是由于MHC i类限制性CD8+T细胞的激活,加上促炎细胞因子IFN-γ、TNF-α和IL-2的分泌增加。此外,树突状细胞的特异性激活通过其共刺激CD80和MHC II类分子的2 - 3倍上调表明。这种方法可能是一种有前途的新策略,为未来临床应用的合理设计癌症疫苗。
A carcinoembryonic antigen (CEA)-based DNA vaccine, adsorbed onto cationic microparticles of poly(dl-lactide-co-glycolide) (PLG) induced tumor-protective immunity against a lethal challenge of MC38-CEA colon carcinoma cells in CEA-transgenic mice that was more potent than that of the corresponding naked DNA vaccine. Boosting with a plasmid encoding murine GM-CSF increased the vaccine’s efficacy leading to a complete rejection of tumor cells in 50% of mice. This effect was due to activation of MHC class I-restricted CD8+T cells coupled with an increased secretion of proinflammatory cytokines IFN-γ, TNF-α and IL-2. Also, specific activation of dendritic cells was indicated by a two–three-fold upregulation of their costimulatory CD80 and MHC class II molecules. This approach may be a promising new strategy for the rational design of cancer vaccines for future clinical applications.