Inhibition of melanoma growth by subcutaneous administration of hTERTC27 viral cocktail in C57BL/6 mice.
Inhibition of melanoma growth by subcutaneous administration of hTERTC27 viral cocktail in C57BL/6 mice.
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DOI：
10.1371/journal.pone.0012705
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发表时间：
2010-09-13
期刊：
影响因子：
3.7
通讯作者：
Lin MC
中科院分区：
文献类型：
--
作者：
Huo L;Yao H;Wang X;Wong GW;Kung HF;Lin MC
hTERTC27 是人端粒酶逆转录酶的 27 kDa C 端多肽，此前已被证明可以降低 HeLa 细胞的致瘤性并抑制裸鼠中异种移植的胶质母细胞瘤的生长。尽管hTERTC27的异位表达上调了参与细胞凋亡、细胞周期和免疫反应的基因，但hTERTC27诱导肿瘤抑制的机制尚未完全阐明。由于hTERT被确定为通用的肿瘤相关抗原，我们假设hTERTC27通过激活抗肿瘤免疫反应来抑制体内肿瘤生长。免疫活性 C57BL/6 小鼠用于小鼠 B16 黑色素瘤模型。给患有 B16 黑色素瘤的小鼠注射表达 hTERTC27 的 rAAV-/rAdv 病毒混合物，并在病毒混合物治疗后监测肿瘤生长。血液和脾细胞分别用于测定细胞因子的水平和免疫细胞的活性。皮下注射单剂量的1.5×1011 vg rAAV-hTERTC27和2.5×109 pfu rAdv-hTERTC27病毒混合物（rAAV-/rAdv-hTERTC27）显着抑制B16肿瘤生长。 rAAV-/rAdv-hTERTC27 治疗显着增加了小鼠中 NK 细胞的数量和细胞毒性，并且通过腹膜内注射抗 GM1 抗体选择性消除小鼠中的 NK 细胞群，消除了 rAAV-/rAdv-hTERTC27 给药诱导的黑色素瘤生长抑制。通过施用 rAAV-/rAdv-hTERTC27 激活 NK 细胞对于抑制小鼠模型中黑色素瘤的生长至关重要。
hTERTC27 is a 27 kDa C-terminal polypeptide of human telomerase reverse transcriptase that has previously been shown to reduce tumorigenicity of HeLa cells and suppress growth of xenografted glioblastoma in nude mice. Although ectopic expression of hTERTC27 upregulated genes that are involved in apoptosis, cell cycle, and immune response, the mechanism for hTERTC27-induced tumor suppression has not been completely elucidated. Since hTERT was identified as a universal tumor-associated antigen, we hypothesize that hTERTC27 inhibits tumor growth in vivo through activation of anti-tumor immune response. Immunocopetent C57BL/6 mice were used for mouse B16 melanoma model. Mice bearing B16 melanoma were administered rAAV-/rAdv viral cocktail expressing hTERTC27, and tumor growth was monitored after viral cocktail treatment. Blood and splenocytes were used to determine the level of cytokines and the activity of immune cells, respectively. B16 tumor growth was significantly inhibited by subcutaneous administration of a single dose of 1.5×1011 vg rAAV-hTERTC27 and 2.5×109 pfu rAdv-hTERTC27 viral cocktail (rAAV-/rAdv-hTERTC27). The population and cytotoxicity of NK cells in the mice were significantly augmented by rAAV-/rAdv-hTERTC27 treatment, and selective depletion of the NK cell population in mice by intraperitoneal injection of anti-GM1 antibody abrogated the growth suppression of melanoma induced by rAAV-/rAdv-hTERTC27 administration. Activation of NK cells by administration of rAAV-/rAdv-hTERTC27 is critical for growth suppression of melanoma in mouse model.
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影响因子：
6.4
作者：
Ng, S. S. M.;Gao, Y.;Lin, M. C. M.
通讯作者：
Lin, M. C. M.
影响因子：
5.4
作者：
Ferrari, FK;Samulski, T;Samulski, RJ
通讯作者：
Samulski, RJ
DOI：
10.1016/j.bbrc.2004.03.098
发表时间：
2004-05-07
影响因子：
3.1
作者：
Chen, Y;Luk, KDK;Kung, HF
通讯作者：
Kung, HF
影响因子：
6.4
作者：
Duthie, Malcolm S.;Kahn, Stuart J.
通讯作者：
Kahn, Stuart J.
影响因子：
8.4
作者：
Kim, NW
通讯作者：
Kim, NW