Therapy of cancer by cytokines mediated by gene therapy approach

	Therapy of cancer by cytokines mediated by gene therapy approach
	Qian, C; Liu, XY; Prieto, J
刊名	CELL RESEARCH
	2006
卷号	16 期号:2 页码:182-188
关键词	gene therapy cancer cytokines vectors adenovirus
通讯作者	Qian, C (reprint author), Zhejiang Sci Tech Univ, Xinyuan Inst Med & Biotechnol, Sch Life Sci, Hangzhou, Peoples R China.,cqian@unav.es
英文摘要	Gene therapy offers a new approach for treatment of cancer. Transfer of genes encoding immunostimulatory cytokines has been used with remarkable success to eliminate cancer in animals. However, clinical trials in patients with this strategy had limited efficacy. Therefore, improvement of gene transfer vector system is necessary. A hybrid viral vector, consisting of SFV replicon with either murine IL-12 or reporter LacZ gene, was constructed. This hybrid vector showed specificity and high level of expression in HCC both in vitro and in vivo. In a rat orthotropic liver tumor model, treatment of established tumors by the hybrid vector with mIL-12 gene resulted in a strong anti-tumor activity without accompanying toxicity. Subsequently, a helper-dependent adenovirus vectors containing a mifepristone (RU486) inducible system was constructed for controlled and liver-specific expression of human interleukin 12 (hIL-12) (HD-Ad/RUhIL-12) and mouse IL-12 (mIL-12) (HD-Ad/RUinIL-12). Data showed that high and sustained serum levels of hIL-12 could be attained by continuing administration of RU486 every 12 or 24 h. Repetitive induction of hIL-12 could be obtained over, at least, a period of 48 weeks after a single injection of HD-Ad/RUhIL-12. Treatment of liver metastases with of HD-Ad/RUmIL-12 plus RU846 resulted in complete tumor regression in all animals. Then, different cytokine genes were inserted into conditional replicative adenoviruses vectors (also called oncolytic adenovirus). Replication of adenovirus in tumor cells would kill tumor cells and release viruses, which infect surrounding tumor cells. The combination of cytopathic effect by oncolytic adenovirus and biological effect of transgene would exert strong antitumor activity. These new types of vectors may provide a potent and safe tool for cancer gene therapy.
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	ONCOLYTIC ADENOVIRAL VECTOR ; ENDOTHELIAL GROWTH-FACTOR ; EXPRESSION IN-VIVO ; HEPATOCELLULAR-CARCINOMA ; INTRATUMORAL INJECTION ; LIVER-CANCER ; PHASE-I ; TRANSGENE EXPRESSION ; ANTITUMOR IMMUNITY ; COLON-CANCER
收录类别	SCI
语种	英语
WOS记录号	WOS:000237176900010
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1670]
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	Qian, C,Liu, XY,Prieto, J. Therapy of cancer by cytokines mediated by gene therapy approach[J]. CELL RESEARCH,2006,16(2):182-188.
APA	Qian, C,Liu, XY,&Prieto, J.(2006).Therapy of cancer by cytokines mediated by gene therapy approach.CELL RESEARCH,16(2),182-188.
MLA	Qian, C,et al."Therapy of cancer by cytokines mediated by gene therapy approach".CELL RESEARCH 16.2(2006):182-188.