Tumor Infarction in Mice by Antibody-Directed Targeting of Tissue
Factor to Tumor Vasculature
Xianming Huang,
*
Grietje Molema,
*
Steven King,
Linda Watkins,
Thomas S. Edgington,
Philip E. Thorpe
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.
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.
To whom correspondence should be addressed.
