Targeting of breast metastases using a viral gene vector with tumour-selective transcription.
Authors
Rajendran, SimonCollins, Sara
van Pijkeren, Jan P
O'Hanlon, Deirdre
O'Sullivan, Gerald C
Tangney, Mark
Affiliation
Cork Cancer Research Centre, Mercy University Hospital, Cork, Ireland.Issue Date
2012-01-31T16:40:01ZMeSH
Adenocarcinoma/genetics/pathology/*therapyAnimals
Breast Neoplasms/genetics/*pathology/*therapy
Dependovirus/*genetics
Female
Flow Cytometry
*Gene Therapy
Gene Transfer Techniques
Genetic Vectors/*administration & dosage
Humans
Liver Neoplasms/genetics/secondary/*therapy
Mice
Mice, Nude
Promoter Regions, Genetic
Receptors, CXCR4/genetics
Transcription, Genetic
Transduction, Genetic
Tumor Cells, Cultured
Metadata
Show full item recordCitation
Anticancer Res. 2011 May;31(5):1627-35.Journal
Anticancer researchPubMed ID
21617219Abstract
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 AND METHODS: 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.Language
engISSN
1791-7530 (Electronic)0250-7005 (Linking)