Use of @entity40085 promoter to develop an adenoviral system that confers transgene expression in XXXX cells but not in normal mesothelial cells.

@entity43 @entity1 @entity5344 @entity7791 @entity40085 @entity1492 @entity1778 @entity2834 @entity526
The objective of this study was to develop an adenoviral vector system that would generate a pattern of expression of exogenous therapeutic genes appropriate for the treatment of @entity43 . For this purpose, we have generated a replication-deficient recombinant adenoviral vector, AdLPLacZ, which contains the @entity1 @entity40085 ( @entity40085 ) promoter ( @entity40085 -P) driving the @entity526 LacZ gene. @entity40085 is constitutively expressed at high levels in malignant epithelial cells but is not expressed in normal tissues, except at low levels in mature hematopoietic cells. Because adenoviral vectors infect early hematopoietic multilineage precursor cells only poorly or not at all, this vector would be of use in the peritoneal cavity and in vitro for marrow purging. We first analyzed the expression of the LacZ reporter gene in @entity5344 cell lines, normal fibroblasts, and @entity1778 cell lines using the adenoviral vector in which the LacZ gene is governed by the LP-P promoter (AdLPLacZ) or in which the LacZ gene is governed by the cytomegalovirus ( @entity2834 ) promoter (AdCMVLacZ). We found equivalent and high levels of expression of @entity7791 ( @entity7791 ) by AdLPLacZ and AdCMVLacZ vectors in the @entity5344 cell lines as well as in a @entity1492 cell line, indicating that the adenoviral vectors infected these cells and expressed their transgenes equally with the LP and @entity2834 promoters. Expression of the LacZ gene with the @entity2834 vector but not with the LP-P vector was observed in experiments with normal fibroblasts, indicating that the vectors infected the cells, but that the LP-P was not active within them. In hematopoietic cells such as U937 cells, no measurable @entity7791 activity was detected in cells infected either by AdLPLacZ or by AdCMVLacZ, indicating that the adenoviral vectors were not infecting the cells. Although @entity7791 activity was observed in fresh ascitic @entity43 cells after infection with adenoviral vectors containing @entity2834 or the LP promoters, @entity7791 activity was detected in a portion of a biopsy of normal peritoneum when the tissues were exposed to the AdCMVLacZ vector, but not when tissues were exposed to the AdLPLacZ vector. These results suggest that the transcription of therapeutic genes in cells infected by the AdLP vectors would be restricted to LP expression-positive @entity43 cells but would not be seen in the normal mesothelial cells of the peritoneal cavity. This possibility implies that adenoviral vectors carrying therapeutic genes driven by the LP-P would be of use for the @entity43 .
