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Titolo:
Targeting of adenovirus to endothelial cells by a bispecific single-chain diabody directed against the adenovirus fiber knob domain and human endoglin (CD105)
Autore:
Nettelbeck, DM; Miller, DW; Jerome, V; Zuzarte, M; Watkins, SJ; Hawkins, RE; Muller, R; Kontermann, RE;
Indirizzi:
Univ Marburg, Inst Mol Biol & Tumorforsch, D-35033 Marburg, Germany Univ Marburg Marburg Germany D-35033 morforsch, D-35033 Marburg, Germany Paterson Inst Canc Res, Dept Med Oncol, Christie CRC Res Ctr, Manchester M20 4BX, Lancs, England Paterson Inst Canc Res Manchester Lancs England M204BX X, Lancs, England
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 6, volume: 3, anno: 2001,
pagine: 882 - 891
SICI:
1525-0016(200106)3:6<882:TOATEC>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN SOLID TUMORS; MONOCLONAL-ANTIBODIES; REDUCED TOXICITY; PHAGE LIBRARIES; SCID MICE; VECTORS; CANCER; EXPRESSION; VASCULATURE; DELIVERY;
Keywords:
adenovirus; bispecific antibodies; single-chain diabody; phage display; endothelial cells; gene therapy; vascular targeting;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Kontermann, RE Univ Marburg, Inst Mol Biol & Tumorforsch, Emil Mannkopff Str 2, D-35033 Marburg, Germany Univ Marburg Emil Mannkopff Str 2 Marburg Germany D-35033
Citazione:
D.M. Nettelbeck et al., "Targeting of adenovirus to endothelial cells by a bispecific single-chain diabody directed against the adenovirus fiber knob domain and human endoglin (CD105)", MOL THER, 3(6), 2001, pp. 882-891

Abstract

The use of adenoviruses for antivascular cancer gene therapy is limited bytheir low transduction efficiency for endothelial cells. We have developeda recombinant bispecific antibody as a molecular bridge, linking the adenovirus capsid to the endothelial cell surface protein endoglin, for vasculartargeting 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) boundspecifically 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 EDC-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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 07:29:47