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

Title data

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. Vol. 3 (June 2001) Issue 6 . - pp. 882-891.
ISSN 1525-0024
DOI: https://doi.org/10.1006/mthe.2001.0342

Official URL: Volltext

Abstract in another language

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.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Engineering Science
Faculties > Faculty of Engineering Science > Chair Process Biotechnology
Faculties
Result of work at the UBT: No
DDC Subjects: 500 Science
500 Science > 500 Natural sciences
600 Technology, medicine, applied sciences
600 Technology, medicine, applied sciences > 610 Medicine and health
Date Deposited: 26 Feb 2016 10:48
Last Modified: 26 Feb 2016 10:48
URI: https://eref.uni-bayreuth.de/id/eprint/31078