Targeting of breast metastases using a viral gene vector with tumour-selective transcription.
Anticancer Res
; 31(5): 1627-35, 2011 May.
Article
en En
| MEDLINE
| ID: mdl-21617219
ABSTRACT
BACKGROUND:
Adeno-associated virus (AAV) vectors have significant potential as gene delivery vectors for cancer gene therapy. However, broad AAV2 tissue tropism results in nonspecific gene expression. MATERIALS ANDMETHODS:
We investigated use of the C-X-C chemokine receptor type 4 (CXCR4) promoter to restrict AAV expression to tumour cells, in subcutaneous MCF-7 xenograft mouse models of breast cancer and in patient samples, using bioluminescent imaging and flow cytometric analysis.RESULTS:
Higher transgene expression levels were observed in subcutaneous MCF-7 tumours relative to normal tissue (muscle) using the CXCR4 promoter, unlike a ubiquitously expressing Cytomegalovirus promoter construct, with preferential AAVCXCR4 expression in epithelial tumour and CXCR4-positive cells. Transgene expression following intravenously administered AAVCXCR4 in a model of liver metastasis was detected specifically in livers of tumour bearing mice. Ex vivo analysis using patient samples also demonstrated higher AAVCXCR4 expression in tumour compared with normal liver tissue.CONCLUSION:
This study demonstrates for the first time, the potential for systemic administration of AAV2 vector for tumour-selective gene therapy.
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Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Terapia Genética
/
Adenocarcinoma
/
Dependovirus
/
Vectores Genéticos
/
Neoplasias Hepáticas
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Año:
2011
Tipo del documento:
Article