In vitro anti-tumor immune response induced by dendritic cells transfected with hTERT recombinant adenovirus
In vitro anti-tumor immune response induced by dendritic cells transfected with hTERT recombinant adenovirus
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DOI：
10.1016/j.bbrc.2006.10.165
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发表时间：
2006-12-29
影响因子：
3.1
通讯作者：
Yang, Shi-Ming
中科院分区：
文献类型：
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作者：
Chen, Ling;Liang, Guang-Ping;Yang, Shi-Ming
用编码转基因的重组复制缺陷型腺病毒（Ad）载体转导是将基因转移到人树突状细胞（DC）中的有效方法。多项研究表明，人端粒酶逆转录酶基因（hTERT）的表位可以产生针对恶性肿瘤的特异性CTL。本研究利用DNA重组技术构建了hTERT重组腺病毒（rAd-hTERT）。我们发现rAd-hTERT转染的人树突状细胞在体外能有效地诱导hTERT特异性细胞毒性T淋巴细胞（CTL）对抗多种肿瘤细胞系，这些肿瘤细胞系为hTERT阳性且HLA-A2匹配。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。进一步的研究表明，rAd-hTERT转导的DC在与hTERT阳性和HLA-A2匹配的肿瘤细胞系共培养时，可以增加效应细胞分泌IFN-γ。这些数据表明，hTERT疫苗可以在体外以HLA-A2限制的方式诱导针对表达hTERT的各种肿瘤细胞的抗肿瘤免疫。用rAd-hTERT转导DC为肿瘤免疫治疗提供了一个很好的机会。(c)2006年爱思唯尔公司All rights reserved.
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. (c) 2006 Elsevier Inc. All rights reserved.