Expression of Coxsackie adenovirus receptor and alphav-integrin does not correlate with adenovector targeting in vivo indicating anatomical vector barriers

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.…”

Hypoxia-mediated tumour targeting

“…Following intravenous delivery of the Ad.CMVLacZ vector we detected strong b-gal expression, particularly in the liver, which is known to express high levels of the Coxsackie/Adenoviral Receptor (CAR). 22 In contrast, we found that the OBHRE promoter had a very low basal activity in organs such as liver, spleen, lung and kidney such that b-gal expression in the liver was 1000-fold lower than that driven by the CMV promoter. However, the OBHRE promoter mediated strong b-gal expression in the tumour microenvironment, comparable to that driven by the CMV promoter.…”

Transductional targeting of adenovirus vectors for gene therapy

“…30 Adenovirus vector biodistribution in vivo, however, is not determined solely by receptor biodistribution. 31 Intravenous administration of Ad results in accumulation in the liver, spleen, heart, lung and kidneys of mice, although these tissues may not necessarily be the highest in CAR expression. 32,33 This is true with regard to the liver in particular, which sequesters the majority of systemically administered Ad particles via hepatic macrophage (Kupffer cell) uptake 34 and hepatocyte transduction, 35 leading to Ad-mediated inflammation and liver toxicity.…”