Titlebar

Bibliografische Daten exportieren
Literatur vom gleichen Autor
plus auf ERef Bayreuth
plus bei Google Scholar

 

Targeting of Adenovirus to Endothelial Cells by a Bispecific Single-Chain Diabody Directed against the Adenovirus Fiber Knob Domain and Human Endoglin (CD105)

Titelangaben

Nettelbeck, Dirk M. ; Miller, Daniel W. ; Jérôme, Valérie ; Zuzarte, Marylou ; Watkins, Sarah J. ; Hawkins, Robert E. ; Müller, Rolf ; Kontermann, Roland E.:
Targeting of Adenovirus to Endothelial Cells by a Bispecific Single-Chain Diabody Directed against the Adenovirus Fiber Knob Domain and Human Endoglin (CD105).
In: Molecular Therapy. Bd. 3 (Juni 2001) Heft 6 . - S. 882-891.
ISSN 1525-0024
DOI: https://doi.org/10.1006/mthe.2001.0342

Volltext

Link zum Volltext (externe URL): Volltext

Abstract

The use of adenoviruses for antivascular cancer gene therapy is limited by their low transduction efficiency for endothelial cells. We have developed a recombinant bispecific antibody as a molecular bridge, linking the adenovirus capsid to the endothelial cell surface protein endoglin, for vascular targeting of adenoviruses. Endoglin (CD105), a component of the transforming growth factor beta receptor complex, represents a promising target for antivascular cancer therapy. Endoglin is expressed predominantly on endothelial cells and is upregulated in angiogenic areas of tumors. We isolated single-chain Fv fragments directed against human endoglin from a human semisynthetic antibody library. One of the isolated scFv fragments (scFv C4) bound specifically to various proliferating primary endothelial cells or cell lines including HUVEC, HDMEC, HMVEC, and HMEC. ScFv C4 was therefore used to construct a bispecific single-chain diabody directed against endoglin and the adenovirus fiber knob domain (scDb EDG-Ad). This bispecific molecule mediated enhanced and selective adenovirus transduction of HUVECs, which was independent from binding to the coxsackievirus and adenovirus receptor (CAR) and alpha(v)-integrins. Thus, adenovirus infection was redirected to a new cellular receptor (CD105) and cell entry pathway. These results demonstrate the utility of bispecific single-chain diabodies, which can be produced in large quantities in bacteria, for the retargeting of adenoviruses in cancer gene therapy.

Weitere Angaben

Publikationsform: Artikel in einer Zeitschrift
Begutachteter Beitrag: Ja
Institutionen der Universität: Fakultäten > Fakultät für Ingenieurwissenschaften
Fakultäten > Fakultät für Ingenieurwissenschaften > Lehrstuhl Bioprozesstechnik
Fakultäten
Titel an der UBT entstanden: Nein
Themengebiete aus DDC: 500 Naturwissenschaften und Mathematik
500 Naturwissenschaften und Mathematik > 500 Naturwissenschaften
600 Technik, Medizin, angewandte Wissenschaften
600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
Eingestellt am: 26 Feb 2016 10:48
Letzte Änderung: 26 Feb 2016 10:48
URI: https://eref.uni-bayreuth.de/id/eprint/31078