CNTO 859, a humanized anti-tissue factor monoclonal antibody, is a potent inhibitor of breast cancer metastasis and tumor growth in xenograft models.
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.
Ngo
Cam V
CV
Discovery Research, Centocor Inc., 145 King of Prussia Road, Radnor, PA 19087, USA.
Picha
Kristen
K
McCabe
Francis
F
Millar
Hillary
H
Tawadros
Richard
R
Tam
Susan H
SH
Nakada
Marian T
MT
Anderson
G Mark
GM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000517:prevention & control / Q000556:secondary; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008815:Mice, Inbred Strains; D013925:Thromboplastin / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D013925:Thromboplastin