Genetically Engineered Intracellular Single-Chain Antibodies in Gene Therapy

2002 ◽  
Vol 22 (2) ◽  
pp. 191-212 ◽  
Author(s):  
Guadalupe Bilbao ◽  
Juan Luis Contreras ◽  
David T Curiel
1998 ◽  
Vol 11 (1) ◽  
pp. 42-56 ◽  
Author(s):  
Bruce A. Bunnell ◽  
Richard A. Morgan

SUMMARY Gene therapy is being investigated as an alternative treatment for a wide range of infectious diseases that are not amenable to standard clinical management. Approaches to gene therapy for infectious diseases can be divided into three broad categories: (i) gene therapies based on nucleic acid moieties, including antisense DNA or RNA, RNA decoys, and catalytic RNA moieties (ribozymes); (ii) protein approaches such as transdominant negative proteins and single-chain antibodies; and (iii) immunotherapeutic approaches involving genetic vaccines or pathogen-specific lymphocytes. It is further possible that combinations of the aforementioned approaches will be used simultaneously to inhibit multiple stages of the life cycle of the infectious agent.


2019 ◽  
Vol 13 ◽  
pp. 86-98 ◽  
Author(s):  
Chris P. Hughes ◽  
Neil M.J. O’Flynn ◽  
Maureen Gatherer ◽  
Michelle E. McClements ◽  
Jennifer A. Scott ◽  
...  

2003 ◽  
pp. 121-149
Author(s):  
Guadalupe Bilbao ◽  
Jesus Gomez-Navarro ◽  
Keizo Kazano ◽  
Juan Luis Contreras ◽  
David T. Curiel

2009 ◽  
pp. NA-NA ◽  
Author(s):  
Deniz Gur ◽  
Suling Liu ◽  
Anurag Shukla ◽  
Stephanie C Pero ◽  
Max S Wicha ◽  
...  

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.


2007 ◽  
Vol 131 (2) ◽  
pp. S251-S252
Author(s):  
Symon Riedstra ◽  
Gonçalo Leite ◽  
Carolina Ferreira ◽  
Francisco Brás Gomes ◽  
Paulo M.P. Costa ◽  
...  

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