title: Targeting of breast metastases using a viral gene vector with tumour-selective transcription.
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.
  
  
  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.
  
  
  CONCLUSIONS
  This study demonstrates for the first time, the potential for systemic administration of AAV2 vector for tumour-selective gene therapy.
authors: Cork Cancer Research Centre, Mercy University Hospital, Cork, Ireland.
authors: Simon
authors: S
authors: Rajendran
authors: Sara
authors: S
authors: Collins
authors: Jan P
authors: JP
authors: van Pijkeren
authors: Deirdre
authors: D
authors: O'Hanlon
authors: Gerald C
authors: GC
authors: O'Sullivan
authors: Mark
authors: M
authors: Tangney