scholarly journals Vascular Gene Transfer from Metallic Stent Surfaces Using Adenoviral Vectors Tethered through Hydrolysable Cross-linkers

Author(s):  
Ilia Fishbein ◽  
Scott P. Forbes ◽  
Richard F. Adamo ◽  
Michael Chorny ◽  
Robert J. Levy ◽  
...  
2002 ◽  
Vol 76 (6) ◽  
pp. 2753-2762 ◽  
Author(s):  
Victor W. van Beusechem ◽  
Jacques Grill ◽  
D. C. Jeroen Mastenbroek ◽  
Thomas J. Wickham ◽  
Peter W. Roelvink ◽  
...  

ABSTRACT The application of adenoviral vectors in cancer gene therapy is hampered by low receptor expression on tumor cells and high receptor expression on normal epithelial cells. Targeting adenoviral vectors toward tumor cells may improve cancer gene therapy procedures by providing augmented tumor transduction and decreased toxicity to normal tissues. Targeting requires both the complete abolition of native tropism and the addition of a new specific binding ligand onto the viral capsid. Here we accomplished this by using doubly ablated adenoviral vectors, lacking coxsackievirus-adenovirus receptor and αv integrin binding capacities, together with bispecific single-chain antibodies targeted toward human epidermal growth factor receptor (EGFR) or the epithelial cell adhesion molecule. These vectors efficiently and selectively targeted both alternative receptors on the surface of human cancer cells. Targeted doubly ablated adenoviral vectors were also very efficient and specific with primary human tumor specimens. With primary glioma cell cultures, EGFR targeting augmented the median gene transfer efficiency of doubly ablated adenoviral vectors 123-fold. Moreover, EGFR-targeted doubly ablated vectors were selective for human brain tumors versus the surrounding normal brain tissue. They transduced organotypic glioma and meningioma spheroids with efficiencies similar to those of native adenoviral vectors, while exhibiting greater-than-10-fold-reduced background levels on normal brain explants from the same patients. As a result, EGFR-targeted doubly ablated adenoviral vectors had a 5- to 38-fold-improved tumor-to-normal brain targeting index compared to native vectors. Hence, single-chain targeted doubly ablated adenoviral vectors are promising tools for cancer gene therapy. They should provide an improved therapeutic index with efficient tumor transduction and effective protection of normal tissue.


2004 ◽  
pp. 147-164
Author(s):  
Jean-Noel Gouze ◽  
Martin J. Stoddart ◽  
Elvire Gouze ◽  
Glyn D. Palmer ◽  
Steven C. Ghivizzani ◽  
...  

2001 ◽  
Vol 50 (1) ◽  
pp. 67
Author(s):  
Seung Ho Choi ◽  
Kyung Ho Park ◽  
Ja Young Seol ◽  
Chul Gyu Yoo ◽  
Choon Taek Lee ◽  
...  

2001 ◽  
Vol 164 (5) ◽  
pp. 866-872 ◽  
Author(s):  
MARTIN KOLB ◽  
MARK INMAN ◽  
PETER J. MARGETTS ◽  
TOM GALT ◽  
JACK GAULDIE

2006 ◽  
Vol 33 (3) ◽  
pp. 391-398 ◽  
Author(s):  
Gang Niu ◽  
Richard D. Anderson ◽  
Mark T. Madsen ◽  
Michael M. Graham ◽  
Larry W. Oberley ◽  
...  

Circulation ◽  
2002 ◽  
Vol 105 (9) ◽  
pp. 1104-1109 ◽  
Author(s):  
Claudius Teupe ◽  
Sergio Richter ◽  
Beate Fisslthaler ◽  
Voahanginirina Randriamboavonjy ◽  
Christian Ihling ◽  
...  

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