scholarly journals Gene Therapy of Glioblastoma Multiforme - Clinical Experience on the Use of Adenoviral Vectors

10.5772/21055 ◽  
2011 ◽  
Author(s):  
Thomas Wirth ◽  
Seppo Yla-Herttual
Keyword(s):  
Gene Therapy ◽  
Glioblastoma Multiforme ◽  
Clinical Experience ◽  
Adenoviral Vectors

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

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 ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Brain Tumors ◽  
Human Brain ◽  
Cancer Gene Therapy ◽  
Adenoviral Vectors ◽  
Receptor Expression ◽  
Normal Brain ◽  
Cancer Gene ◽  
Single Chain

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.

Clinical Experience with Gene Therapy in Older Spinal Muscular Atrophy Patients

2021 ◽  
Author(s):  
Susan E. Matesanz ◽  
Vanessa Battista ◽  
Jean Flickinger ◽  
Jennifer N. Jones ◽  
Elizabeth A. Kichula
Keyword(s):  
Gene Therapy ◽  
Spinal Muscular Atrophy ◽  
Clinical Experience ◽  
Muscular Atrophy

Gutless Adenoviral Vectors - Promising Tools for Gene Therapy

2002 ◽  
Vol 34 (2) ◽  
pp. 95-100 ◽  
Author(s):  
Alicja Jozkowicz ◽  
J. Dulak ◽  
J. Nanobashvili ◽  
P. Polterauer ◽  
M. Prager ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Adenoviral Vectors
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