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Science 24 January 1997:
Vol. 275. no. 5299, pp. 547 - 550
DOI: 10.1126/science.275.5299.547
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Tumor Infarction in Mice by Antibody-Directed Targeting of Tissue Factor to Tumor Vasculature

Xianming Huang, * Grietje Molema, *dagger Steven King, Linda Watkins, Thomas S. Edgington, Philip E. Thorpe ddagger

Selective occlusion of tumor vasculature was tested as a therapy for solid tumors in a mouse model. The formation of blood clots (thrombosis) within the tumor vessels was initiated by targeting the cell surface domain of human tissue factor, by means of a bispecific antibody, to an experimentally induced marker on tumor vascular endothelial cells. This truncated form of tissue factor (tTF) had limited ability to initiate thrombosis when free in the circulation, but became an effective and selective thrombogen when targeted to tumor endothelial cells. Intravenous administration of the antibody-tTF complex to mice with large neuroblastomas resulted in complete tumor regressions in 38 percent of the mice.

X. Huang, G. Molema, S. King, L. Watkins, P. E. Thorpe, Department of Pharmacology and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
T. S. Edgington, Departments of Immunology and Vascular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
*   These authors contributed equally to this work.

dagger    Present address: Groningen Utrecht Institute for Drug Exploration, Department of Clinical Immunology, and Department of Pharmacokinetics and Drug Delivery, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, Netherlands.

ddagger    To whom correspondence should be addressed.

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   Abstract »    Full Text »    PDF »
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   Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »


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