A novel conditionally replicative adenovirus vector targeting telomerase-positive tumor cells.

Published

Journal Article

PURPOSE: To develop a novel conditionally replicative adenovirus vector that targets telomerase-positive cancer cells. EXPERIMENTAL DESIGN: A telomerase gene-derived promoter was used to control the expression of the E1a gene so that the E1a gene is only expressed in telomerase-positive tumor cells. In addition, a reporter gene was also engineered into the vector so that its infection and replication can be monitored easily. RESULTS: A novel recombinant adenovirus vector that could selectively replicate in telomerase-positive cancer cells was made successfully. This vector showed active replication in a panel of cancer cells and minimal replication in normal human fibroblast or epithelial cells. The recombinant vector could effectively lyse various cultured tumor cells even at very low multiplicity of infection. The replication efficiency in tumor cells is over 10(3)-fold more than normal fibroblast and epithelial cells. In s.c. tumor models, the newly developed telomerase-selective adenovirus vectors exhibited significantly more virus replication and reporter gene expression. CONCLUSIONS: The telomerase-targeted adenovirus vector has significant potential as an oncolytic virus as well as a tumor-specific therapeutic gene delivery vehicle.

Full Text

Duke Authors

Cited Authors

  • Huang, Q; Zhang, X; Wang, H; Yan, B; Kirkpatrick, J; Dewhrist, MW; Li, C-Y

Published Date

  • February 2004

Published In

Volume / Issue

  • 10 / 4

Start / End Page

  • 1439 - 1445

PubMed ID

  • 14977847

Pubmed Central ID

  • 14977847

International Standard Serial Number (ISSN)

  • 1078-0432

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.ccr-03-0122

Language

  • eng