CAR-dependent and CAR-independent pathways of adenovirus vector–mediated gene transfer and expression in human fibroblasts

CAR is a cell–cell adhesion protein in human cancer cells and is expressionally modulated by dexamethasone, TNFα, and TGFβ

“…7 For human cancer cells, CAR has been shown to be homogeneously distributed throughout the cell membrane. 26,27 In these studies, cells were either stained as singular cells or under non-cell-cell contact-forming conditions. 26,27 The same staining pattern was observed on singular cancer cells or on viable cancer cells immunostained at low temperatures, a condition where formation of cell-cell contacts was reduced.…”

“…26,27 In these studies, cells were either stained as singular cells or under non-cell-cell contact-forming conditions. 26,27 The same staining pattern was observed on singular cancer cells or on viable cancer cells immunostained at low temperatures, a condition where formation of cell-cell contacts was reduced. When cancer cells were prefixed before immunostaining for CAR, we observed an obvious enrichment of CAR at cell-cell contacts.…”

“…A Brüning and IB Runnebaum applied retargeting of adenoviral vectors to integrins, 26,28,29 independent of CAR expression and its localization, can be a promising tool for more efficient gene transfer efficiencies into human cancer cells. Application of cytokines enhancing expression of CAR and integrins preferentially with anti-tumoral activity can contribute to a better therapeutic efficacy in gene therapeutic applications.…”

Efficient repetitive gene delivery to skeletal muscle using recombinant adenovirus vector containing the Coxsackievirus and adenovirus receptor cDNA

“…In some experiments with elevated expression of CAR in mouse and human fibroblasts, the susceptibility to adenovirus infection tended to correlate with CAR expression. 16,26 Subsequently, C2C12 and primary cultured myoblasts with stable expression of retrovirus-induced CAR cDNA were sensitive for adenovirus infection, in vitro and in vivo. 14 In our present study, we showed a similar effect in the myoblast cell lines using rAd containing CAR cDNA.…”

Trans-complementation of vector replication versus Coxsackie-adenovirus-receptor overexpression to improve transgene expression in poorly permissive cancer cells

“…Approaches to improve the gene transfer rate include fiber knob domain modifications [17][18][19][20] or the addition of polycations 21 in order to achieve CAR-independent gene transfer, and overexpression of CAR. 12,13,22 The latter has been reported to increase vector uptake up to 1000-fold in primarily resistant cells such as human dermal fibroblasts. Others found only a five-fold increase for human alveolar macrophages 13 or a five-to sevenfold increase in head and neck squamous cell carcinoma cells.…”