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人端粒酶逆转录酶重组腺病毒转导的树突状细胞在小鼠中诱导抗肿瘤免疫

Induction of anti-tumour immunity by dendritic cells transduced with hTERT recombinant adenovirus in mice.

作者信息

Chen Ling, Tang Xu-Dong, Yu Song-Tao, Ai Zhi-Hua, Fang Dian-Chun, Cai Yong-Guo, Luo Yuan-Hui, Liang Guang-Ping, 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

J Pathol. 2009 Apr;217(5):685-92. doi: 10.1002/path.2493.

Abstract

Dendritic cells (DCs) transfected with recombinant, replication-defective adenovirus (Ad) vectors encoding the human telomerase reverse transcriptase (hTERT) are potent inducers of cytotoxic T lymphocytes (CTLs) and anti-tumour immunity. However, previous studies have mostly been in vitro. In this study, we sought to determine whether DCs transfected with hTERT (DC/Ad-hTERT) could elicit a potent anti-tumour immunogenic response in vivo. We found that murine DCs transfected with recombinant adenovirus encoding the hTERT gene (DC/Ad-hTERT) induced hTERT-specific CTLs in vivo effectively, compared with Ad-LacZ-transduced DC (DC/Ad-LacZ) controls. These hTERT-specific CTLs lysed various tumour cell lines in an hTERT-specific and MHC-I molecule-restricted fashion. We also found that DC/Ad-hTERT could increase antigen-specific T-cell proliferation and augment the number of IFN-gamma secreting T-cells in mice. These data suggest that the DC/Ad-hTERT vaccine may induce anti-tumour immunity against tumour cells expressing hTERT in an MHC-I molecule-restricted fashion in vivo through the augmentation of the hTERT-specific CTL response. The DC/Ad-hTERT vaccine may thus be used as an efficient DC-based tumour vaccine in clinical applications.

摘要

用编码人端粒酶逆转录酶(hTERT)的重组、复制缺陷型腺病毒(Ad)载体转染的树突状细胞(DC)是细胞毒性T淋巴细胞(CTL)和抗肿瘤免疫的有效诱导剂。然而,以往的研究大多是在体外进行的。在本研究中,我们试图确定用hTERT转染的DC(DC/Ad-hTERT)是否能在体内引发有效的抗肿瘤免疫原性反应。我们发现,与Ad-LacZ转导的DC(DC/Ad-LacZ)对照相比,用编码hTERT基因的重组腺病毒转染的小鼠DC(DC/Ad-hTERT)在体内能有效诱导hTERT特异性CTL。这些hTERT特异性CTL以hTERT特异性和MHC-I分子限制的方式裂解各种肿瘤细胞系。我们还发现,DC/Ad-hTERT可以增加小鼠体内抗原特异性T细胞增殖并增加分泌IFN-γ的T细胞数量。这些数据表明,DC/Ad-hTERT疫苗可能通过增强hTERT特异性CTL反应,在体内以MHC-I分子限制的方式诱导针对表达hTERT的肿瘤细胞的抗肿瘤免疫。因此,DC/Ad-hTERT疫苗可作为一种有效的基于DC的肿瘤疫苗用于临床应用。

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