Lister strain vaccinia virus, a potential therapeutic vector targeting hypoxic tumours.
Gene Ther
; 17(2): 281-7, 2010 Feb.
Article
em En
| MEDLINE
| ID: mdl-19890355
ABSTRACT
Hypoxia contributes to the aggressive and treatment-resistant phenotype of pancreatic ductal adenocarcinoma. Oncolytic vaccinia virus has potential as an anti-tumour agent, but the ability to lyse hypoxic tumour cells is vital for clinical efficacy. We hypothesized that unique aspects of the poxvirus life cycle would protect it from attenuation in hypoxic conditions. We characterized and compared the viral protein production, viral replication, cytotoxicity and transgene expression of Lister strain vaccinia virus in a panel of pancreatic cancer cell lines after exposure to normoxic or hypoxic conditions. Viral protein production was not affected by hypoxia, and high viral titres were produced in both normoxic and hypoxic conditions. Interestingly, there was a 3.5-fold (P<0.001) and 20-fold (P<0.0001) increase in viral cytotoxicity for CFPac1 and MiaPaca2 cell lines, respectively, in hypoxic conditions. Cytotoxicity was equivalent in the remaining cell lines. Levels of transgene expression (luciferase reporter gene) from the vaccinia viral vector were comparable, regardless of the ambient oxygen concentration. The present study suggests that the vaccinia virus is a promising vector for targeting pancreatic cancer and potentially other hypoxic tumour types.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vaccinia virus
/
Hipóxia Celular
/
Técnicas de Transferência de Genes
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Terapia Viral Oncolítica
/
Vetores Genéticos
Limite:
Humans
Idioma:
En
Revista:
Gene Ther
Assunto da revista:
GENETICA MEDICA
/
TERAPEUTICA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Reino Unido