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Adenoviral vectors for targeting tumor endothelium

Targeting of adenoviral vector to tumor endothelium has been successfully achieved using different strategies.

Adenobodies, obtained by the fusion of a single chain antibody (S11) and a peptide, were able to bind respectively to the adenoviral fiber knob and to selected endothelial receptors. S11 was able to prevent the binding of adenoviral vectors to its natural CAR receptor thereby avoiding uptake of the virus by unselected cells. The peptides on the other hand were able to guide the virus to the receptors VEGFR2, Tie 2 and integrins av(beta)3. (Anna Rita Bellu, Marieke Geel, Anu Kariat, Marianne G.Rots, Hidde J. Haisma. Selective targeting of adenoviral vectors to endothelial receptors avß3 integrins, VEGF and Tie2 by angio-adenobodies. Submitted.)

A PEG molecule, bi-functional polyethylene glycol, has been shown to shield the adenovirus so that it was not able to bind to CAR and was not recognized by the immunosystem when injected intravenously in animals thereby incrementing the circulation time. The RGD peptide chemically coupled to the PEG molecule was able both in vitro and in vivo to target the pegylated virus to integrins.

Furthermore, the HI loop of the viral fiber knob has been genetically modified for the insertion of peptides such as RGD to target the adenovirus to integrins. This method compared to the non-genetic modifications (adenobodies and pegylation) has the advantage to be a stable modification and is not influenced from external factors.
(Anna Rita Bellu, Yunia Sribudiani, Marieke Geel, Ramon Alemany, Gritje Molema, Hidde J. Haisma. Adenoviral targeting of the tumor endothelium using three different approaches. Submitted).

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