Signaling antibodies complexed with adenovirus circumvent CAR and integrin interactions and improve gene delivery

Histone deacetylase inhibitors upregulate expression of the coxsackie adenovirus receptor (CAR) preferentially in bladder cancer cells

“…13 Here, we demonstrate that CAR downregulation is an epigenetic phenomenon, which can be reversed with histone deacetylase inhibitors (HDACI) in vitro in our bladder cancer cells. Importantly, normal urothelial cells or low-grade CAR-positive bladder cancer cells do not demonstrate induction of CAR expression under the same conditions.…”

Efficient and Selective Gene Transfer into Primary Human Brain Tumors by Using Single-Chain Antibody-Targeted Adenoviral Vectors with Native Tropism Abolished

“…Targeting toward the bombesin/gastrin-releasing peptide receptor, on the other hand, appeared to still depend on penton baseactivated endocytosis (17). Inhibitors of tyrosine kinase receptor-and PI3K-mediated signal transduction had contradictory effects on the targeted AdV transduction in different studies (16,25), leaving the role of signal transduction in the targeted AdV uptake pathway unresolved. All of these previous studies used neutralizing peptides, antibodies, or Ad protein or pharmacologic signal transduction inhibitors to interfere with penton base-initiated signaling.…”

“…This suggested that while ␣ v integrin interaction augments native adenovirus infection, it might not be involved in targeted AdV uptake. Integrin-independent targeted AdV transduction has so far been reported only with targeting moieties comprising active mitogenic ligands for tyrosine kinase growth factor receptors, including basic fibroblast growth factor, insulin-like growth factor 1, EGF, and tumor necrosis factor alpha (9,25). Targeting toward the bombesin/gastrin-releasing peptide receptor, on the other hand, appeared to still depend on penton baseactivated endocytosis (17).…”

Transgene expression is increased by photochemically mediated transduction of polycation-complexed adenoviruses

“…17,18 The penton base of such particles is competent to interact with cellular integrins, and the particles are capable of infecting cells trough a CARindependent pathway although with a severely reduced infectivity. Gene delivery by fiberless virus can be enhanced by retargeting the vector, 19 showing that particles lacking the fiber at least to some extent are able to accomplish steps subsequent to uptake.…”