Tumor infarction in mice by antibody-directed targeting of tissue factor to tumor vasculature.

Abstract

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.

• Authors: X Huang, G Molema, S King, L Watkins, T S Edgington, P E Thorpe
• Journal: Science (New York, N.Y.) (Science) Vol. 275 Issue 5299 Pg. 547-50 (Jan 24 1997) ISSN: 0036-8075 [Print] United States
• PMID: 8999802 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies
• Histocompatibility Antigens Class II
• Immunoconjugates
• Thromboplastin

Topics

• Animals
• Antibodies (immunology)
• Blood Coagulation
• Endothelium, Vascular (immunology)
• Histocompatibility Antigens Class II (immunology, metabolism)
• Humans
• Immunoconjugates (administration & dosage, metabolism, therapeutic use)
• Injections, Intravenous
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neuroblastoma (blood supply, drug therapy, pathology)
• Thromboplastin (administration & dosage, metabolism, therapeutic use)
• Tumor Cells, Cultured