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

doi:10.1016/j.taap.2014.08.008

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	Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus
	Qi, Yanxin 1,2; Guo, Huanhuan 2,3; Hu, Ningning 2,4; He, Dongyun 2,4; Zhang, Shi 2,5; Chu, Yunjie 7; Huang, Yubin 1; Li, Xiao 2,4; Sun, Lili 6; Jin, Ningyi 2,4
刊名	TOXICOLOGY AND APPLIED PHARMACOLOGY
	2014-10-15
卷号	280 期号:2 页码:362-369
关键词	Conditionally Replicating Adenovirus Apoptin Human Telomerase Reverse Transcriptase Safety Evaluation
ISSN号	0041-008X
DOI	10.1016/j.taap.2014.08.008
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.
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000344444700018
内容类型	期刊论文
源URL	[http://ir.iccas.ac.cn/handle/121111/52411]
专题	中国科学院化学研究所
通讯作者	Li, Xiao
作者单位	1.Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Polymer Phys & Chem, Changchun 130022, PR, Peoples R China 2.Acad Mil Med Sci, Inst Mil Vet, Changchun 130122, Peoples R China 3.Changchun Brother Biotech Co Ltd, Changchun 130000, Peoples R China 4.Key Lab Jilin Prov Zoonosis Prevent & Control, Changchun 130122, Peoples R China 5.Jilin Univ, Sch Clin Med, Changchun 130001, Peoples R China 6.Tumor Hosp Jilin Prov, Dept Head & Neck Surg, Changchun 130012, Peoples R China 7.Changchun Univ Tradit Chinese Med, Affiliated Hosp, Changchun 130021, Peoples R China
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.