|
|
Blood, 14 May 2009, Vol. 113, No. 20, pp. 5019-5027.
Prepublished online as a Blood First Edition Paper on January 28, 2009; DOI 10.1182/blood-2008-04-150318.
 Previous Article | Next Article 
Submitted April 11, 2008
Accepted December 3, 2008
Infarction of tumor vessels by NGR-peptide directed targeting of tissue factor. Experimental results and first-in-man experience
Ralf Bieker, Torsten Kessler, Christian Schwoppe, Teresa Padro, Thorsten Persigehl, Christoph Bremer, Johannes Dreischaluck, Astrid Kolkmeyer, Walter Heindel, Rolf M. Mesters, and Wolfgang E. Berdel*
Department of Medicine / Hematology and Oncology, University of Muenster, Muenster, Germany
Department of Clinical Radiology, University of Muenster, Muenster, Germany
* Corresponding author; email: berdel{at}uni-muenster.de.
We induced thrombosis of blood vessels in solid tumors in mice by a fusion protein consisting of the extracellular domain of tissue factor (truncated tissue factor, tTF) and the peptide GNGRAHA, targeting aminopeptidase N (CD13) and the integrin  v 3 (CD51/CD61) on tumor vascular endothelium. The designed fusion protein tTF-NGR retained its thrombogenic activity as demonstrated by coagulation assays. In vivo studies in mice bearing established human adenocarcinoma (A549), melanoma (M21) and fibrosarcoma (HT1080) revealed that systemic administration of tTF-NGR induced partial or complete thrombotic occlusion of tumor vessels as shown by histological analysis. tTF-NGR but not untargeted tTF induced significant tumor growth retardation or regression in all three types of solid tumors. Thrombosis induction in tumor vessels by tTF-NGR was also shown by contrast enhanced magnetic resonance imaging (MRI). In the human fibrosarcoma xenograft model MRI revealed a significant reduction of tumor perfusion by administration of tTF-NGR. Clinical first-in-man application of low dosages of this targeted coagulation factor revealed good tolerability and decrease of tumor perfusion as measured by MRI. Targeted thrombosis in the tumor vasculature induced by tTF-NGR may be a promising strategy for the treatment of cancer.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Articles in Blood Online:
-
NGR and isoDGR are separate moieties binding to different receptors
- Gian-Paolo Rizzardi and Claudio Bordignon
Blood 2009 113: 5366.
[Full Text]
[PDF]
-
Response: NGR and isoDGR are separate moieties binding to different receptors
- Christian Schwöppe, Ralf Bieker, Rolf M. Mesters, and Wolfgang E. Berdel
Blood 2009 113: 5367.
[Full Text]
[PDF]
-
Flipping the wound that doesn't heal: the upside of coagulation in cancer
- Beverly A. Teicher
Blood 2009 113: 4827-4828.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
R. S. Kasthuri, M. B. Taubman, and N. Mackman
Role of Tissue Factor in Cancer
J. Clin. Oncol.,
October 10, 2009;
27(29):
4834 - 4838.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G.-P. Rizzardi and C. Bordignon
NGR and isoDGR are separate moieties binding to different receptors
Blood,
May 21, 2009;
113(21):
5366 - 5366.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Teicher
Flipping the wound that doesn't heal: the upside of coagulation in cancer
Blood,
May 14, 2009;
113(20):
4827 - 4828.
[Full Text]
[PDF]
|
|
|
|
|
