Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus

	Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus
	Qi, Yanxin ; Guo, Huanhuan ; Hu, Ningning ; He,Dongyun ; Zhang,Shi ; Chu,Yunjie ; Huang,Yubin ; Li,Xiao ; Sun,Lili ; Jin,Ningyi
刊名	toxicology and applied pharmacology
	2014
卷号	280 期号:2 页码:362-369
关键词	REPLICATION-SELECTIVE ADENOVIRUS PHASE-II TRIAL GENE-THERAPY NECK-CANCER CLINICAL-TRIALS APOPTIN ONYX-015 CARCINOMA ANIMALS SAFETY
通讯作者	li,x
英文摘要	clinical studies have demonstrated that conditionally replicating adenovirus is safe. we constructed an oncolytic adenovirus, ad-htert-e1a-apoptin, using a cancer-specific promoter (human telomerase reverse transcriptase promoter, htertp) and a cancer cell-selective apoptosis-inducing gene (apoptin). ad-htert-e1a-apoptin was proven effective both in vitro and in vivo in our previous study. in this study, the preclinical safety profiles of ad-htert-e1a-apoptin in animal models were investigated. at doses of 5.0 x 10(8), 2.5 x 10(9), and 1.25 x 10(10) viral particles (vp)/kg, ad-htert-e1a-apoptin had no adverse effects on mouse behavior, muscle cooperation, sedative effect, digestive system, and nervous systems, or on beagle cardiovascular and respiratory systems at 5.0 x 10(8), 2.5 x 10(9), and 1.25 x 10(10) vp/kg doses. in acute toxicity tests in mice, the maximum tolerated dose > 5 x 10(10) vp/kg. there was no inflammation or ulceration at the injection sites within two weeks. in repeat-dose toxicological studies, the no observable adverse effect levels of ad-htert-e1a-apoptin in rats (1.25 x 10(10) vp/kg) and beagles (2.5 x 10(9) vp/kg) were 62.5- and 12.5-fold of the proposed clinical dose, respectively. the anti-virus antibody was produced in animal sera. bone marrow examination revealed no histopathological changes. guinea pigs sensitized by three repeated intraperitoneal injections of 135 x 10(10) vp/ml ad-htert-e1a-apoptin each and challenged by one intravenous injection of 1.67 x 10(8) vp/kg ad-htert-e1a-apoptin did not exhibit any sign of systemic anaphylaxis. our data from different animal models suggest that ad-htert-e1a-apoptin is a safe anti-tumor therapeutic agent. (c) 2014 elsevier inc. all rights reserved.
收录类别	SCI
语种	英语
公开日期	2015-10-27
内容类型	期刊论文
源URL	[http://ir.ciac.jl.cn/handle/322003/57301]
专题	长春应用化学研究所_长春应用化学研究所知识产出_期刊论文
推荐引用方式 GB/T 7714	Qi, Yanxin,Guo, Huanhuan,Hu, Ningning,et al. Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus[J]. toxicology and applied pharmacology,2014,280(2):362-369.
APA	Qi, Yanxin.,Guo, Huanhuan.,Hu, Ningning.,He,Dongyun.,Zhang,Shi.,...&Jin,Ningyi.(2014).Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus.toxicology and applied pharmacology,280(2),362-369.
MLA	Qi, Yanxin,et al."Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus".toxicology and applied pharmacology 280.2(2014):362-369.