Cancer Research AACR Membership Advances in Breast Cancer Research
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nilsson, F.
Right arrow Articles by Neri, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nilsson, F.
Right arrow Articles by Neri, D.
[Cancer Research 61, 711-716, January 15, 2001]
© 2001 American Association for Cancer Research

Experimental Therapeutics

Targeted Delivery of Tissue Factor to the ED-B Domain of Fibronectin, a Marker of Angiogenesis, Mediates the Infarction of Solid Tumors in Mice1

Fredrik Nilsson, Hartwig Kosmehl, Luciano Zardi and Dario Neri1

Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich, CH-8057 Zurich, Switzerland [F. N., D. N.]; Institute of Pathology, Friedrich Schiller University, D-07740 Jena, Germany [H. K.]; and Laboratory of Cell Biology, Istituto Nazionale per la Ricerca sul Cancro, I-16132 Genoa, Italy [L. Z.]

The selective thrombosis of tumor blood vessels, leading to the starvation and subsequent death of tumor cells, is an attractive anticancer strategy. Here we report that a fusion protein, consisting of an antibody fragment specific for the oncofoetal ED-B domain of fibronectin fused to the extracellular domain of tissue factor, selectively targets tumor blood vessels in vivo. Furthermore, this fusion protein mediates the complete and selective infarction of three different types of solid tumors in mice. At the highest doses administered, complete tumor eradication was observed in 30% of the mice treated without apparent side effects. These results are of therapeutic relevance because the ED-B domain of fibronectin, a naturally occurring marker of angiogenesis identical in mouse and man, is expressed in the majority of aggressive solid tumors but is undetectable in normal vessels and tissues.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
S. Fernando and B. S. Fletcher
Targeting Tumor Endothelial Marker 8 in the Tumor Vasculature of Colorectal Carcinomas in Mice
Cancer Res., June 15, 2009; 69(12): 5126 - 5132.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
R. Bieker, T. Kessler, C. Schwoppe, T. Padro, T. Persigehl, C. Bremer, J. Dreischaluck, A. Kolkmeyer, W. Heindel, R. M. Mesters, et al.
Infarction of tumor vessels by NGR-peptide-directed targeting of tissue factor: experimental results and first-in-man experience
Blood, May 14, 2009; 113(20): 5019 - 5027.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. Marlind, M. Kaspar, E. Trachsel, R. Sommavilla, S. Hindle, C. Bacci, L. Giovannoni, and D. Neri
Antibody-Mediated Delivery of Interleukin-2 to the Stroma of Breast Cancer Strongly Enhances the Potency of Chemotherapy
Clin. Cancer Res., October 15, 2008; 14(20): 6515 - 6524.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. Wagner, P. Schulz, A. Scholz, B. Wiedenmann, and A. Menrad
The Targeted Immunocytokine L19-IL2 Efficiently Inhibits the Growth of Orthotopic Pancreatic Cancer
Clin. Cancer Res., August 1, 2008; 14(15): 4951 - 4960.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
A. Van Langendonckt, J. Donnez, S. Defrere, G. A.J. Dunselman, and P. G. Groothuis
Antiangiogenic and vascular-disrupting agents in endometriosis: pitfalls and promises
Mol. Hum. Reprod., May 1, 2008; 14(5): 259 - 268.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
G. A.M.S. van Dongen, G. W.M. Visser, M. N. Lub-de Hooge, E. G. de Vries, and L. R. Perk
Immuno-PET: A Navigator in Monoclonal Antibody Development and Applications
Oncologist, December 1, 2007; 12(12): 1379 - 1389.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
T. Persigehl, R. Bieker, L. Matuszewski, A. Wall, T. Kessler, H. Kooijman, N. Meier, W. Ebert, W. E. Berdel, W. Heindel, et al.
Antiangiogenic Tumor Treatment: Early Noninvasive Monitoring with USPIO-enhanced MR Imaging in Mice
Radiology, August 1, 2007; 244(2): 449 - 456.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Kaspar, E. Trachsel, and D. Neri
The Antibody-Mediated Targeted Delivery of Interleukin-15 and GM-CSF to the Tumor Neovasculature Inhibits Tumor Growth and Metastasis
Cancer Res., May 15, 2007; 67(10): 4940 - 4948.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. Moosmayer, D. Berndorff, C.-H. Chang, R. M. Sharkey, A. Rother, S. Borkowski, E. A. Rossi, W. J. McBride, T. M. Cardillo, D. M. Goldenberg, et al.
Bispecific antibody pretargeting of tumor neovasculature for improved systemic radiotherapy of solid tumors.
Clin. Cancer Res., September 15, 2006; 12(18): 5587 - 5595.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
B. M. Tijink, D. Neri, C. R. Leemans, M. Budde, L. M. Dinkelborg, M. Stigter-van Walsum, L. Zardi, and G. A.M.S. van Dongen
Radioimmunotherapy of Head and Neck Cancer Xenografts Using 131I-Labeled Antibody L19-SIP for Selective Targeting of Tumor Vasculature
J. Nucl. Med., July 1, 2006; 47(7): 1127 - 1135.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
S. S. Brack, M. Silacci, M. Birchler, and D. Neri
Tumor-targeting properties of novel antibodies specific to the large isoform of tenascin-C.
Clin. Cancer Res., May 15, 2006; 12(10): 3200 - 3208.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
X. Huang, W.-Q. Ding, J. L. Vaught, R. F. Wolf, J. H. Morrissey, R. G. Harrison, and S. E. Lind
A soluble tissue factor-annexin V chimeric protein has both procoagulant and anticoagulant properties
Blood, February 1, 2006; 107(3): 980 - 986.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
H. Akiyama, K. A. Mohamedali, R. L. e Silva, S. Kachi, J. Shen, C. Hatara, N. Umeda, S. F. Hackett, S. Aslam, M. Krause, et al.
Vascular Targeting of Ocular Neovascularization with a Vascular Endothelial Growth Factor121/Gelonin Chimeric Protein
Mol. Pharmacol., December 1, 2005; 68(6): 1543 - 1550.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. Berndorff, S. Borkowski, S. Sieger, A. Rother, M. Friebe, F. Viti, C. S. Hilger, J. E. Cyr, and L. M. Dinkelborg
Radioimmunotherapy of Solid Tumors by Targeting Extra Domain B Fibronectin: Identification of the Best-Suited Radioimmunoconjugate
Clin. Cancer Res., October 1, 2005; 11(19): 7053s - 7063s.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. Kessler, R. Bieker, T. Padro, C. Schwoppe, T. Persigehl, C. Bremer, M. Kreuter, W. E. Berdel, and R. M. Mesters
Inhibition of Tumor Growth by RGD Peptide-Directed Delivery of Truncated Tissue Factor to the Tumor Vasculature
Clin. Cancer Res., September 1, 2005; 11(17): 6317 - 6324.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
A. Dienst, A. Grunow, M. Unruh, B. Rabausch, J. E. Nor, J. W. U. Fries, and C. Gottstein
Specific Occlusion of Murine and Human Tumor Vasculature by VCAM-1-Targeted Recombinant Fusion Proteins
J Natl Cancer Inst, May 18, 2005; 97(10): 733 - 747.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
J. Smith, R. E. Kontermann, J. Embleton, and S. Kumar
Antibody phage display technologies with special reference to angiogenesis
FASEB J, March 1, 2005; 19(3): 331 - 341.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
C. M. Matter, P. K. Schuler, P. Alessi, P. Meier, R. Ricci, D. Zhang, C. Halin, P. Castellani, L. Zardi, C. K. Hofer, et al.
Molecular Imaging of Atherosclerotic Plaques Using a Human Antibody Against the Extra-Domain B of Fibronectin
Circ. Res., December 10, 2004; 95(12): 1225 - 1233.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
P. Carter, L. Smith, and M. Ryan
Identification and validation of cell surface antigens for antibody targeting in oncology
Endocr. Relat. Cancer, December 1, 2004; 11(4): 659 - 687.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
H. Gourdeau, L. Leblond, B. Hamelin, C. Desputeau, K. Dong, I. Kianicka, D. Custeau, C. Boudreau, L. Geerts, S.-X. Cai, et al.
Antivascular and antitumor evaluation of 2-amino-4-(3-bromo-4,5-dimethoxy-phenyl)-3-cyano-4H-chromenes, a novel series of anticancer agents
Mol. Cancer Ther., November 1, 2004; 3(11): 1375 - 1384.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
P. E. Thorpe
Vascular Targeting Agents as Cancer Therapeutics
Clin. Cancer Res., January 15, 2004; 10(2): 415 - 427.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
L. Borsi, E. Balza, B. Carnemolla, F. Sassi, P. Castellani, A. Berndt, H. Kosmehl, A. Biro, A. Siri, P. Orecchia, et al.
Selective targeted delivery of TNF{alpha} to tumor blood vessels
Blood, December 15, 2003; 102(13): 4384 - 4392.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
S. Christian, J. Pilch, M. E. Akerman, K. Porkka, P. Laakkonen, and E. Ruoslahti
Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels
J. Cell Biol., November 24, 2003; 163(4): 871 - 878.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. S. Palumbo, K. E. Talmage, H. Liu, C. M. La Jeunesse, D. P. Witte, and J. L. Degen
Plasminogen supports tumor growth through a fibrinogen-dependent mechanism linked to vascular patency
Blood, October 15, 2003; 102(8): 2819 - 2827.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. Hu, J. Yan, J. Sharifi, T. Bai, L. A. Khawli, and A. L. Epstein
Comparison of Three Different Targeted Tissue Factor Fusion Proteins for Inducing Tumor Vessel Thrombosis
Cancer Res., August 15, 2003; 63(16): 5046 - 5053.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Halin, V. Gafner, M. E. Villani, L. Borsi, A. Berndt, H. Kosmehl, L. Zardi, and D. Neri
Synergistic Therapeutic Effects of a Tumor Targeting Antibody Fragment, Fused to Interleukin 12 and to Tumor Necrosis Factor {alpha}
Cancer Res., June 15, 2003; 63(12): 3202 - 3210.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Santimaria, G. Moscatelli, G. L. Viale, L. Giovannoni, G. Neri, F. Viti, A. Leprini, L. Borsi, P. Castellani, L. Zardi, et al.
Immunoscintigraphic Detection of the ED-B Domain of Fibronectin, a Marker of Angiogenesis, in Patients with Cancer
Clin. Cancer Res., February 1, 2003; 9(2): 571 - 579.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
P. Castellani, L. Borsi, B. Carnemolla, A. Biro, A. Dorcaratto, G. L. Viale, D. Neri, and L. Zardi
Differentiation between High- and Low-Grade Astrocytoma Using a Human Recombinant Antibody to the Extra Domain-B of Fibronectin
Am. J. Pathol., November 1, 2002; 161(5): 1695 - 1700.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Liu, H. Huang, F. Donate, C. Dickinson, R. Santucci, A. El-Sheikh, R. Vessella, and T. S. Edgington
Prostate-specific Membrane Antigen Directed Selective Thrombotic Infarction of Tumors
Cancer Res., October 1, 2002; 62(19): 5470 - 5475.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Fukuda, N. Yoshida, Y. Kataoka, R.-i. Manabe, Y. Mizuno-Horikawa, M. Sato, K. Kuriyama, N. Yasui, and K. Sekiguchi
Mice Lacking the EDB Segment of Fibronectin Develop Normally but Exhibit Reduced Cell Growth and Fibronectin Matrix Assembly in Vitro
Cancer Res., October 1, 2002; 62(19): 5603 - 5610.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. C. Blakey, F. R. Westwood, M. Walker, G. D. Hughes, P. D. Davis, S. E. Ashton, and A. J. Ryan
Antitumor Activity of the Novel Vascular Targeting Agent ZD6126 in a Panel of Tumor Models
Clin. Cancer Res., June 1, 2002; 8(6): 1974 - 1983.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
K. Porkka, P. Laakkonen, J. A. Hoffman, M. Bernasconi, and E. Ruoslahti
A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo
PNAS, May 28, 2002; 99(11): 7444 - 7449.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. E. J. G. J. Dolmans, A. Kadambi, J. S. Hill, C. A. Waters, B. C. Robinson, J. P. Walker, D. Fukumura, and R. K. Jain
Vascular Accumulation of a Novel Photosensitizer, MV6401, Causes Selective Thrombosis in Tumor Vessels after Photodynamic Therapy
Cancer Res., April 1, 2002; 62(7): 2151 - 2156.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
B. Carnemolla, L. Borsi, E. Balza, P. Castellani, R. Meazza, A. Berndt, S. Ferrini, H. Kosmehl, D. Neri, and L. Zardi
Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix
Blood, March 1, 2002; 99(5): 1659 - 1665.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
C. Halin, L. Zardi, and D. Neri
Antibody-Based Targeting of Angiogenesis
Physiology, August 1, 2001; 16(4): 191 - 194.
[Abstract] [Full Text] [PDF]

Home page
 Vet PatholHome page

Vet. Pathol., May 1, 2001; 38(3): 355 - 355.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2001 by the American Association for Cancer Research.