In vitro anti-tumor immune response induced by dendritic cells transfected with EBV-LMP2 recombinant adenovirus.
In vitro anti-tumor immune response induced by dendritic cells transfected with EBV-LMP2 recombinant adenovirus.
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DOI：
10.1016/j.bbrc.2006.05.214
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发表时间：
2006-09
影响因子：
3.1
通讯作者：
Ying Pan;Jin-kun Zhang;Ling-ye Zhou;J. Zuo;Yi Zeng
中科院分区：
文献类型：
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作者：
Ying Pan;Jin-kun Zhang;Ling-ye Zhou;J. Zuo;Yi Zeng
EB病毒相关性鼻咽癌是中国南部地区的一种高发肿瘤。潜伏膜蛋白2(LMP2)是EBV的一种亚优势抗原。本研究旨在研制基于树突状细胞(DC)的肿瘤疫苗(rAd-LMP2-DC)，并对其生物学特性和免疫功能进行研究。我们的结果表明，LMP2基因转移并没有改变成熟DC的典型形态，成熟DC的典型表型(CD80、CD83和CD86)在rad-LMP2-DC中高表达。Rad-LPM2-DC中LMP2的表达约为84.54%，提示基因转移是有效的。转染树突状细胞可显著促进抗原特异性T细胞增殖。树突状细胞对鼻咽癌细胞的杀伤活性明显高于对照组(p<；0.05)，且随刺激强度的增加而增强。此外，表型分析表明，LMP2特异性CTL由CD4+T细胞和CD8+T细胞组成。这些结果表明，以肿瘤相关病毒抗原为载体的树突状细胞疫苗的研制，可诱导出较强的CTL应答，为EB病毒相关性鼻咽癌的免疫治疗提供了一种新的策略。
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is a high-incidence tumor in southern China. Latent membrane proteins 2 (LMP2) is a subdominant antigen of EBV. The present study was to develop a dendritic cells (DCs)-based cancer vaccine (rAd-LMP2-DC) and to study its biological characteristics and its immune functions. Our results showed that LMP2 gene transfer did not alter the typical morphology of mature DC, and the representative phenotypes of mature DC (CD80, CD83, and CD86) were highly expressed in rAd-LMP2-DCs. The expression of LMP2 in rAd-LPM2-DCs was about 84.54%, which suggested efficient gene transfer. Transfected DCs markedly increased antigen-specific T-cell proliferation. The specific cytotoxicity against NPC cell was significantly higher than that in controls (p<0.05), and enhanced with increased stimulations by transfected DCs. In addition, phenotypic analysis demonstrated that the LMP2-specific CTLs consisted of both CD4+and CD8+T cells. These results showed that development of DC-based vaccine by transfection with malignancy-associated virus antigens could elicit potent CTL response and provide a potential strategy of immunotherapy for EBV-associated NPC.