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利用转染 hTERTC27 重组腺病毒的树突状细胞对小鼠神经胶质瘤进行有效的抗肿瘤免疫。

Effective antitumor immunity against murine gliomas using dendritic cells transduced with hTERTC27 recombinant adenovirus.

机构信息

Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, PR China.

出版信息

Oncol Rep. 2012 Apr;27(4):1163-9. doi: 10.3892/or.2011.1619. Epub 2011 Dec 30.

Abstract

hTERTC27, a 27-kDa hTERT C-terminal polypeptide has been demonstrated to cause hTERT-positive HeLa cell apoptosis and inhibits the growth of mouse melanoma. hTERTC27 has been associated with telomere dysfunction, regulation of gene-regulated apoptosis, the cell cycle and activation of natural killer (NK) cells, but its mechanism of action is not fully understood. Here, we report that dendritic cells (DCs) transduced with hTERTC27 can increase T-cell proliferation, and augment the concentration of interleukin-2 (IL-2) and interferon-γ (IFN-γ) in the supernatants of T cells. It can also induce antigen-specific cytotoxic T lymphocytes (CTL) against glioma cells in vitro. Moreover, hTERTC27 gene-transduced DCs exhibit a very potent cytotoxicity to glioma cells in vivo. It could prolong the survival time and inhibit the growth of glioma-bearing mice. These data suggest that hTERTC27 gene-transduced DCs can efficiently enhance immunity against gliomas in vitro and in vivo.

摘要

hTERTC27 是一种 27kDa 的 hTERT C 端多肽,已被证明可导致 hTERT 阳性的 HeLa 细胞凋亡,并抑制小鼠黑色素瘤的生长。hTERTC27 与端粒功能障碍、基因调控的细胞凋亡、细胞周期和自然杀伤 (NK) 细胞的激活有关,但它的作用机制尚不完全清楚。在这里,我们报告转染 hTERTC27 的树突状细胞 (DC) 可以增加 T 细胞的增殖,并增加 T 细胞上清液中白细胞介素-2 (IL-2) 和干扰素-γ (IFN-γ) 的浓度。它还可以在体外诱导针对神经胶质瘤细胞的抗原特异性细胞毒性 T 淋巴细胞 (CTL)。此外,hTERTC27 基因转染的树突状细胞在体内对神经胶质瘤细胞具有很强的细胞毒性。它可以延长荷瘤小鼠的生存时间并抑制肿瘤的生长。这些数据表明,hTERTC27 基因转染的树突状细胞可以有效地增强体内外对神经胶质瘤的免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f7b/3583520/18e5dbddc589/OR-27-04-1163-g0.jpg

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