Publication

Targeting of breast metastases using a viral gene vector with tumour-selective transcription.

Rajendran, Simon
; 
Collins, Sara
; 
van Pijkeren, Jan P
; 
O'Hanlon, Deirdre
; 
O'Sullivan, Gerald C
; 
Tangney, Mark
Citations
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Author
Rajendran, Simon
 Collins, Sara
 van Pijkeren, Jan P
 O'Hanlon, Deirdre
 O'Sullivan, Gerald C
 Tangney, Mark
Advisors
Editors
Other Contributors
Departments
Cork Cancer Research Centre, Mercy University Hospital, Cork, Ireland.
Date
2012-01-31T16:40:01Z
Date Submitted
Keywords
Other Subjects
Subject Mesh
Adenocarcinoma/genetics/pathology/*therapy
Animals
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
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
URI
https://hdl.handle.net/10147/206352
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 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
eng
Citation
Anticancer Res. 2011 May;31(5):1627-35.
ISSN
1791-7530 (Electronic)
0250-7005 (Linking)
eISSN
ISBN
DOI
PMID
21617219
PMCID
Sponsorships
Funding Sources
Funding Amounts
Grant Identifiers
Methodology
Duration
Ethical Approval
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