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Oncolysis and suppression of tumor growth by a GFP-expressing oncolytic adenovirus controlled by an hTERT and CMV hybrid promoter.

Abstract：

:One of the challenges of oncolytic virotherapy is the inability to easily track or monitor virus activity during treatment. Here we describe the construction and functional characterization of Ad/hTC-GFP-E1, an oncolytic virus whose transgenes GFP and E1A are both under the control of a synthetic promoter (hTC). This promoter consists of sequences from the human telomorase reverse transcriptase promoter and a minimal cytomegalovirus (CMV) early promoter. The tumor-specific expression of E1A and GFP was demonstrated by Western blot and fluorescent microscope analyses, and the tumor-specific cytotoxicity by crystal-violet staining and cell viability assays. Viral replication and tumor cell lysis occurred at multiplicities of infection (MOI) as low as 100 viral particles per cell in sensitive cell lines. No overt cytotoxic effect was observed in normal human fibroblasts, even at MOIs over 2000 vp. The presence of oncolytic vector was easily visualized and quantitated in vitro and in vivo, in correlation with viral replication. Intralesional administration of the virus into subcutaneous H1299 (NSCLC) tumor xenografts significantly suppressed tumor growth and provided a survival benefit. Together, these results demonstrate that an hTERT-specific oncolytic adenovirus expressing an hTERT-specific transgene is applicable for cancer therapy.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Davis JJ,Wang L,Dong F,Zhang L,Guo W,Teraishi F,Xu K,Ji L,Fang B

doi

10.1038/sj.cgt.7700944

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

720-3

issue

7

eissn

0929-1903

issn

1476-5500

pii

7700944

journal_volume

13

pub_type

杂志文章

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