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CNTO 859, a humanized anti‐tissue factor monoclonal antibody, is a potent inhibitor of breast cancer metastasis and tumor growth in xenograft models
Author(s) -
Ngo Cam V.,
Picha Kristen,
McCabe Francis,
Millar Hillary,
Tawadros Richard,
Tam Susan H.,
Nakada Marian T.,
Anderson G. Mark
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22426
Subject(s) - metastasis , cancer research , angiogenesis , medicine , cancer , antibody , in vivo , cancer cell , monoclonal antibody , immunology , biology , microbiology and biotechnology
Thromboembolic complications are frequently associated with advanced cancer. Interestingly, one of the major initiators of blood coagulation, tissue factor (TF), is reported to be overexpressed in several tumor types and can be found on both tumor cells and tumor vasculature. Although the exact mechanisms have yet to be elucidated, TF expressed on tumor cells can trigger intracellular signaling events through various pathways that can lead to tumor angiogenesis, proliferation, and metastasis. There exists preclinical evidence that disruption of TF dependent signaling can effectively inhibit tumor cell migration, metastasis, and angiogenesis. Here, we report for the first time that an antibody to tissue factor can also prevent tumor growth in vivo . Prophylactic administration of CNTO 859, a humanized anti‐human TF antibody, was shown to inhibit experimental lung metastasis of MDA‐MB‐231 human breast carcinoma cells by over 99% compared to a control antibody. Furthermore, therapeutic doses of CNTO 859 were shown to reduce tumor incidence and growth of orthotopically implanted MDA‐MB‐231 cells. © 2006 Wiley‐Liss, Inc.