Increased safety with preserved antitumoral efficacy on hepatocellular carcinoma with dual-regulated oncolytic adenovirus

	Increased safety with preserved antitumoral efficacy on hepatocellular carcinoma with dual-regulated oncolytic adenovirus
	Zhang, Q; Chen, GH; Peng, LH; Wang, XH; Liu, C; Shi, WF; Su, CQ; Wu, HP; Liu, XY; Wu, MC
刊名	CLINICAL CANCER RESEARCH
	2006
卷号	12 期号:21 页码:6523-6531
通讯作者	Qian, QJ (reprint author), Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Lab Viral & Gene Therapy, 225 Changhai Rd, Shanghai 200438, Peoples R China.,qianqj@sino-gene.cn
英文摘要	Purpose: A dual-regulated adenovirus variant CNHK500, in which human telomerase reverse transcriptase promoter drove the adenovirus 5 (Ad5) E1a gene and hypoxia-response promoter controlled the E1b gene, was engineered. This virus has broad anticancer spectrum and higher specificity compared with mono-regulated adenovirus CNHK300. The objective of the current study is to show its antitumor selectivity and therapeutic potential. Experimental Design: The antitumor specificity of human telomerase reverse transcriptase and hypoxia response promoters was evaluated in a panel of tumor and normal cells. Under the control of these promoters, the tumor-selective expression of E1a and E1b genes was evaluated. Further in vitro antitumor specificity and potency of this virus were characterized by viral replication and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Subsequently, hepatocellular carcinoma xenografts were established to evaluate CNHK500 antitumor efficacy in vivo by different routes of virus administration and different dosages. Results: Human telomerase reverse transcriptase and hypoxia response promoters were activated in a tumor-selective manner or under hypoxia treatment in a broad panel of cells. Selective adenoviral early gene expression, efficient viral replication, and oncolysis were observed in all tested cancer cells with more attenuated replication capacity in normal cells. Significant regression of hepatocellular carcinoma xenografts and prolonged survival were observed by either i.t. or i.v. administration. Conclusions: CNHK500 greatly reduced side effects in normal cells via dual control of adenoviral essential genes while still preserving potent antitumor efficacy on broad-spectrum cancer cells in vitro and in vivo. It can be used as a powerful therapeutic agent not only for liver cancers but also for other solid tumors.
学科主题	Oncology
类目[WOS]	Oncology
关键词[WOS]	GENE-VIRAL THERAPY ; CANCER-THERAPY ; REPLICATIVE ADENOVIRUS ; ANTICANCER AGENTS ; TUMOR-CELLS ; TELOMERASE ; HYPOXIA ; EXPRESSION ; PROMOTER ; VIRUSES
收录类别	SCI
语种	英语
WOS记录号	WOS:000241935100030
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1796]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Zhang, Q,Chen, GH,Peng, LH,et al. Increased safety with preserved antitumoral efficacy on hepatocellular carcinoma with dual-regulated oncolytic adenovirus[J]. CLINICAL CANCER RESEARCH,2006,12(21):6523-6531.
APA	Zhang, Q.,Chen, GH.,Peng, LH.,Wang, XH.,Liu, C.,...&Qian, QJ.(2006).Increased safety with preserved antitumoral efficacy on hepatocellular carcinoma with dual-regulated oncolytic adenovirus.CLINICAL CANCER RESEARCH,12(21),6523-6531.
MLA	Zhang, Q,et al."Increased safety with preserved antitumoral efficacy on hepatocellular carcinoma with dual-regulated oncolytic adenovirus".CLINICAL CANCER RESEARCH 12.21(2006):6523-6531.