Infarction of solid Hodgkin's tumors in mice by antibody-directed targeting of tissue factor to tumor vasculature

Sophia Ran, Boning Gao, Steve Duffy, Linda Watkins, Neal Rote, Philip E. Thorpe

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Pages (from-to)4646-4653
Number of pages8
JournalCancer Research
Volume58
Issue number20
StatePublished - Oct 15 1998

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Vascular Cell Adhesion Molecule-1
Thromboplastin
Hodgkin Disease
Infarction
Phosphatidylserines
Antibodies
Neoplasms
Lung
Thrombosis
Vascular Endothelium
Tumor Biomarkers
Endothelial Cells
Monoclonal Antibodies
Vascular Tissue Neoplasms
SCID Mice
Venules
Endothelium
Anti-Idiotypic Antibodies
Safety
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Infarction of solid Hodgkin's tumors in mice by antibody-directed targeting of tissue factor to tumor vasculature. / Ran, Sophia; Gao, Boning; Duffy, Steve; Watkins, Linda; Rote, Neal; Thorpe, Philip E.

In: Cancer Research, Vol. 58, No. 20, 15.10.1998, p. 4646-4653.

Research output: Contribution to journalArticle

Ran, S, Gao, B, Duffy, S, Watkins, L, Rote, N & Thorpe, PE 1998, 'Infarction of solid Hodgkin's tumors in mice by antibody-directed targeting of tissue factor to tumor vasculature', Cancer Research, vol. 58, no. 20, pp. 4646-4653.
Ran, Sophia ; Gao, Boning ; Duffy, Steve ; Watkins, Linda ; Rote, Neal ; Thorpe, Philip E. / Infarction of solid Hodgkin's tumors in mice by antibody-directed targeting of tissue factor to tumor vasculature. In: Cancer Research. 1998 ; Vol. 58, No. 20. pp. 4646-4653.
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