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Effective gene-viral therapy for telomerase-positive cancers by selective replicative-competent adenovirus combining with endostatin gene
- Source :
- Cancer research. 64(15)
- Publication Year :
- 2004
-
Abstract
- Gene-viral therapy, which uses replication-selective transgene-expressing viruses to manage tumors, can exploit the virtues of gene therapy and virotherapy and overcome the limitations of conventional gene therapy. Using a human telomerase reverse transcriptase-targeted replicative adenovirus as an antiangiogenic gene transfer vector to target new angiogenesis and making use of its unrestrained proliferation are completely new concepts in tumor management. CNHK300-mE is a selective replication transgene-expressing adenovirus constructed to carry mouse endostatin gene therapeutically. Infection with CNHK300-mE was associated with selective replication of the adenovirus and production of mouse endostatin in telomerase-positive cancer cells. Endostatin secreted from a human gastric cell line, SGC-7901, infected with CNHK300-mE was significantly higher than that infected with nonreplicative adenovirus Ad-mE in vitro (800 ± 94.7 ng/ml versus 132.9 ± 9.9 ng/ml) and in vivo (610 ± 42 ng/ml versus 126 ± 13 ng/ml). Embryonic chorioallantoic membrane assay showed that the mouse endostatin secreted by CNHK300-mE inhibited angiogenesis efficiently and also induced distortion of pre-existing vasculature. CNHK300-mE exhibited a superior suppression of xenografts in nude mice compared with CNHK300 and Ad-mE. In summary, we provided a more efficient gene-viral therapy strategy by combining oncolysis with antiangiogenesis.
- Subjects :
- Cancer Research
Telomerase
Angiogenesis
Genetic enhancement
Genetic Vectors
Transplantation, Heterologous
Mice, Nude
Biology
medicine.disease_cause
Virus Replication
Adenoviridae
Mice
Allantois
Stomach Neoplasms
Neoplasms
medicine
Animals
Humans
Virotherapy
Mice, Inbred BALB C
Neovascularization, Pathologic
Genetic Therapy
Endostatins
Oncology
Viral replication
Cell culture
Cancer research
Endothelium, Vascular
Endostatin
Chickens
Subjects
Details
- ISSN :
- 00085472
- Volume :
- 64
- Issue :
- 15
- Database :
- OpenAIRE
- Journal :
- Cancer research
- Accession number :
- edsair.doi.dedup.....d687fab81130a163fc367aa1b3264207