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人端粒酶逆转录酶重组腺病毒转染树突状细胞诱导的体外抗肿瘤免疫反应

In vitro anti-tumor immune response induced by dendritic cells transfected with hTERT recombinant adenovirus.

作者信息

Chen Ling, Liang Guang-Ping, Tang Xu-Dong, Chen Ting, Cai Yong-Guo, Fang Dian-Chun, Yu Song-Tao, Luo Yuan-Hui, Yang Shi-Ming

机构信息

Institute of Gastroenterology of PLA, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.

出版信息

Biochem Biophys Res Commun. 2006 Dec 29;351(4):927-34. doi: 10.1016/j.bbrc.2006.10.165. Epub 2006 Nov 7.

Abstract

Transduction with recombinant, replication-defective adenoviral (Ad) vectors encoding a transgene is an efficient method for gene transfer into human dendritic cells (DC). Several studies have demonstrated that epitopes of the human telomerase reverse transcriptase gene (hTERT) can produce CTLs specific for malignant tumors. In this study, we constructed an hTERT recombinant adenovirus (rAd-hTERT) using DNA recombination. We found that human dendritic cells transduced with rAd-hTERT could effectively induce hTERT-specific cytotoxic T lymphocytes (CTLs) in vitro against various tumor cell lines, which were hTERT-positive and HLA-A2 matched. We also found that these hTERT-specific CTLs could not lyse autologous lymphocytes with low telomerase activity. Further studies revealed that rAd-hTERT transduced DCs could increase secretion of IFN-gamma by effector cells when they were co-cultured with hTERT-positive and HLA-A2 matched tumor cell lines. These data suggest that an hTERT vaccine can induce anti-tumor immunity against various tumor cells expressing hTERT in a HLA-A2-restricted fashion in vitro. The transduction of DCs with rAd-hTERT offers a great opportunity in cancer immunotherapy.

摘要

用编码转基因的重组、复制缺陷型腺病毒(Ad)载体进行转导是将基因导入人树突状细胞(DC)的一种有效方法。多项研究表明,人端粒酶逆转录酶基因(hTERT)的表位可产生针对恶性肿瘤的细胞毒性T淋巴细胞(CTL)。在本研究中,我们利用DNA重组构建了一种hTERT重组腺病毒(rAd-hTERT)。我们发现,用rAd-hTERT转导的人树突状细胞在体外可有效诱导hTERT特异性细胞毒性T淋巴细胞(CTL),以对抗各种hTERT阳性且HLA-A2匹配的肿瘤细胞系。我们还发现,这些hTERT特异性CTL不能裂解端粒酶活性低的自体淋巴细胞。进一步研究表明,当rAd-hTERT转导的DC与hTERT阳性且HLA-A2匹配的肿瘤细胞系共培养时,可增加效应细胞分泌γ干扰素。这些数据表明,hTERT疫苗在体外可通过HLA-A2限制的方式诱导针对各种表达hTERT的肿瘤细胞的抗肿瘤免疫。用rAd-hTERT转导DC在癌症免疫治疗中提供了一个很好的机会。

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