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

被引:14
|
作者
Yuan, Sujing [1 ]
Fang, Xianlong [1 ]
Xu, Yanni [2 ]
Ni, Aimin [1 ]
Liu, Xin-Yuan [1 ]
Chu, Liang [1 ,3 ]
机构
[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China
[2] Northwest Agr & Forestry Univ, Coll Life Sci, Yangling 712100, Peoples R China
[3] Xuzhou Med Coll, Inst Canc, Jiangsu Ctr Collaborat & Innovat Canc Biotherapy, Xuzhou 221002, Peoples R China
基金
上海市自然科学基金;
关键词
oncolytic adenovirus; HAb18; CD147; interleukin; 24; hepatocellular carcinoma; IN-VITRO; CANCER; THERAPY; CD147; MDA-7/IL-24; APOPTOSIS; INVASION; METASTASIS; EFFICIENT; GROWTH;
D O I
10.18632/oncotarget.11134
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:60491 / 60502
页数:12
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