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Evaluation of anti-VEGFR-3 specific scFv antibodies as potential therapeutic and diagnostic tools for tumor lymph-angiogenesis


Zehnder-Fjällman, A H M; Marty, C; Halin, C; Hohn, A; Schibli, R; Ballmer-Hofer, K; Schwendener, R (2007). Evaluation of anti-VEGFR-3 specific scFv antibodies as potential therapeutic and diagnostic tools for tumor lymph-angiogenesis. Oncology Reports, 18(4):933-941.

Abstract

Vascular endothelial growth factor receptor-3 (VEGFR-3) plays a major role in lymph-angiogenesis, tumor growth and metastatic tumor cell dissemination. The receptor is over-expressed on lymphatic vessels in the vicinity of tumors and on the tumor vasculature and therefore may be an excellent target for an effective cancer intervention. We generated and characterized single chain antibody fragments (scFv) recognizing VEGFR-3 by phage display technology and expression in P. pastoris and analyzed selected antibodies in vitro and in vivo. The scFvs were functionalized by the introduction of cysteines at the C-terminal end of the proteins. The scFvs are species cross-specific and bind to recombinant human and mouse VEGFR-3. ScFv AFC5 showed specific tumor accumulation in an hVEGFR-3 expressing F9 terato-carcinoma mouse model, which was also used for tumor visualization by combined single proton emission computed tomography (SPECT/CT) and immunohistochemical analysis. This antibody also inhibited binding of hVEGF-C to its receptor and reduced proliferation of human lymphatic endothelial cells. Thus, the generated VEGFR-3 specific scFv antibodies represent a valuable tool for novel cancer therapies and diagnostic applications.

Vascular endothelial growth factor receptor-3 (VEGFR-3) plays a major role in lymph-angiogenesis, tumor growth and metastatic tumor cell dissemination. The receptor is over-expressed on lymphatic vessels in the vicinity of tumors and on the tumor vasculature and therefore may be an excellent target for an effective cancer intervention. We generated and characterized single chain antibody fragments (scFv) recognizing VEGFR-3 by phage display technology and expression in P. pastoris and analyzed selected antibodies in vitro and in vivo. The scFvs were functionalized by the introduction of cysteines at the C-terminal end of the proteins. The scFvs are species cross-specific and bind to recombinant human and mouse VEGFR-3. ScFv AFC5 showed specific tumor accumulation in an hVEGFR-3 expressing F9 terato-carcinoma mouse model, which was also used for tumor visualization by combined single proton emission computed tomography (SPECT/CT) and immunohistochemical analysis. This antibody also inhibited binding of hVEGF-C to its receptor and reduced proliferation of human lymphatic endothelial cells. Thus, the generated VEGFR-3 specific scFv antibodies represent a valuable tool for novel cancer therapies and diagnostic applications.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research

04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:May 2007
Deposited On:08 Sep 2008 09:27
Last Modified:11 Sep 2016 07:16
Publisher:Spandidos
ISSN:1021-335X
Official URL:http://www.spandidos-publications.com/or/article.jsp?article_id=or_18_4_933
PubMed ID:17786357
Permanent URL: http://doi.org/10.5167/uzh-2956

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