RRC ID |
38532
|
Author |
Cao X, Yang M, Wei RC, Zeng Y, Gu JF, Huang WD, Yang DQ, Li HL, Ding M, Wei N, Zhang KJ, Xu B, Liu XR, Qian QJ, Liu XY.
|
Title |
Cancer targeting Gene-Viro-Therapy of liver carcinoma by dual-regulated oncolytic adenovirus armed with TRAIL gene.
|
Journal |
Gene Ther
|
Abstract |
Liver cancer is a common and aggressive malignancy, but available treatment approaches remain suboptimal. Cancer targeting Gene-Viro-Therapy (CTGVT) has shown excellent anti-tumor effects in a preclinical study. CTGVT takes advantage of both gene therapy and virotherapy by incorporating an anti-tumor gene into an oncolytic virus vector. Potent anti-tumor activity is achieved by virus replication and exogenous expression of the anti-tumor gene. A dual-regulated oncolytic adenoviral vector designated Ad·AFP·E1A·E1B (Δ55) (Ad·AFP·D55 for short thereafter) was constructed by replacing the native viral E1A promoter with the simian virus 40 enhancer/α-fetoprotein (AFP) composite promoter (AFPep) based on an E1B-55K-deleted construct, ZD55. Ad·AFP·D55 showed specific replication and cytotoxicity in AFP-positive hepatoma cells. It also showed enhanced safety in normal cells when compared with the mono-regulated vector ZD55. To improve the anti-hepatoma activities of the virus, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene was introduced into Ad·AFP·D55. Ad·AFP·D55-TRAIL exhibited remarkable anti-tumor activities in vitro and in vivo. Treatment with Ad·AFP·D55-TRAIL can induce both autophagy owing to the Ad·AFP·D55 vector and caspase-dependent apoptosis owing to the TRAIL protein. Therefore, Ad·AFP·D55-TRAIL could be a potential anti-hepatoma agent with anti-tumor activities due to AFP-specific replication and TRAIL-induced apoptosis.
|
Volume |
18(8)
|
Pages |
765-77
|
Published |
2011-8-1
|
DOI |
10.1038/gt.2011.16
|
PII |
gt201116
|
PMID |
21412282
|
MeSH |
Adenoviridae / genetics*
Animals
Apoptosis
Autophagy
Bystander Effect
Carcinoma, Hepatocellular / therapy*
Cell Line, Tumor
Genetic Therapy / methods*
Genetic Vectors
Humans
Liver Neoplasms / therapy*
Mice
Mice, Nude
Oncolytic Virotherapy / methods*
Oncolytic Viruses / genetics*
TNF-Related Apoptosis-Inducing Ligand / genetics*
alpha-Fetoproteins / genetics
|
IF |
4.128
|
Times Cited |
29
|
WOS Category
|
MEDICINE, RESEARCH & EXPERIMENTAL
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
GENETICS & HEREDITY
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
Resource |
Human and Animal Cells |
HuH-7(RCB1366)
HuH-6(RCB1367) |