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一种表达HAb18和白细胞介素24基因的溶瘤腺病毒在肝癌细胞中表现出增强的抗肿瘤活性。

An oncolytic adenovirus that expresses the HAb18 and interleukin 24 genes exhibits enhanced antitumor activity in hepatocellular carcinoma cells.

作者信息

Yuan Sujing, Fang Xianlong, Xu Yanni, Ni Aimin, Liu Xin-Yuan, Chu Liang

机构信息

State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P. R. China.

College of Life Sciences, Northwest Agriculture and Forestry University, Yangling 712100, P. R. China.

出版信息

Oncotarget. 2016 Sep 13;7(37):60491-60502. doi: 10.18632/oncotarget.11134.

Abstract

Hepatocellular carcinoma (HCC) is characterized by alterations in multiple genes. High expression of CD147 on the surface of HCC cells promotes proliferation. The monoclonal antibody HAb18 recognizes CD147. We constructed an oncolytic adenoviral vector to express HAb18 (ZD55-HAb18) in HCC cells. Interleukin 24 (IL24) was co-expressed through the use of an F2A linker. ZD55-HAb18-IL24 decreased HCC cell viability to a greater degree than either ZD55-HAb18 or ZD55-IL24 alone. ZD55-HAb18-IL24 also induced apoptosis and autophagy in PLC/PRF/5 HCC cells. Intratumoral injection of ZD55-HAb18-IL24 repressed tumor growth in a PLC/PRF/5 xenograft model. Our results suggest that antibody-antitumor gene conjugation elicited a stronger antitumor effect than the antibody alone, and that this strategy could broaden the applications of antibody-based therapies in HCC.

摘要

肝细胞癌(HCC)的特征是多个基因发生改变。HCC细胞表面CD147的高表达促进增殖。单克隆抗体HAb18可识别CD147。我们构建了一种溶瘤腺病毒载体,用于在HCC细胞中表达HAb18(ZD55-HAb18)。通过使用F2A连接子共表达白细胞介素24(IL24)。ZD55-HAb18-IL24比单独的ZD55-HAb18或ZD55-IL24更能降低HCC细胞活力。ZD55-HAb18-IL24还可诱导PLC/PRF/5 HCC细胞发生凋亡和自噬。在PLC/PRF/5异种移植模型中,瘤内注射ZD55-HAb18-IL24可抑制肿瘤生长。我们的结果表明,抗体-抗肿瘤基因偶联物比单独的抗体产生更强的抗肿瘤作用,并且该策略可拓宽基于抗体的疗法在HCC中的应用。

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