Infarction of Solid Hodgkin's Tumors in Mice by Antibody-directed Targeting of Tissue Factor to Tumor Vasculature

摘要: We demonstrated previously that selective thrombosis of the blood vessels solid tumors in mice can be achieved by targeting extracellular domain tissue factor means an antibody to experimentally induced marker on tumor vascular endothelium. In present study, we extend this finding a naturally occurring endothelium, cell adhesion molecule-1 (VCAM-1). VCAM-1 is expressed endothelial cells Hodgkin's disease and various humans. It absent from normal tissues mice, with exception heart lungs, where it venules. A monoclonal murine was covalently linked human create "coaguligand." After i.v. administration severe combined immunodeficient bearing tumors, coaguligand localized selectively VCAM-1-expressing vessels, caused those retarded growth. The also lungs but did not induce these sites. An immunohistochemical evaluation distribution anti-phosphatidylserine (PS) showed PS, whereas lacked PS. lack thrombotic effect lung may because PS needed provide procoagulant surface upon which coagulation complexes assemble. requirement for coincident expression targeted endothelium probably contributes selectivity action safety coaguligands.