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Experimental and Molecular Therapeutics 20: Advances in Cancer Therapeutics

CSF-1 antibody chemosensitizes human breast cancer in nude mice

Patrick Paulus, E. Richard Stanley and Seyedhossein Aharinejad
Patrick Paulus
Vienna Medical University, Vienna, Austria and Albert Einstein College of Medicine, New York, NY
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E. Richard Stanley
Vienna Medical University, Vienna, Austria and Albert Einstein College of Medicine, New York, NY
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Seyedhossein Aharinejad
Vienna Medical University, Vienna, Austria and Albert Einstein College of Medicine, New York, NY
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DOI:  Published April 2006
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Proc Amer Assoc Cancer Res, Volume 47, 2006

Abstract

2430

Breast cancer remains a serious health care concern with an incidence that has continued to increase over the last two decades. Overexpression of colony-stimulating factor (CSF)-1 and its receptor in breast cancer is correlated with poor prognosis. Based on the hypothesis that blockade of CSF-1 would be beneficial in breast cancer treatment, we developed murinized, antigen binding fragments (Fab) linked to polyethylene glycol (PEG) against mouse (host) CSF-1. Mice bearing human MCF-7 breast cancer xenografts were treated with combination chemotherapy (CMF; cyclophosphamide 100 mg/kg, methotrexate 50 mg/kg, 5-fluoro-uracil 100 mg/kg) cycled twice i.p., anti-CSF-1 Fab (4 mg/kg i.p.) cycled every three days for 14 days, combined CMF and anti-CSF-1 Fab, or with Ringer’s solution. CSF-1 Fab alone suppressed tissue CSF-1 and retarded tumor growth by 40% compared to controls or CMF treated mice (P < 0.0001). Importantly, in combination with CMF, CSF-1 Fab chemosensitized MCF-7 xenografts, suppressing tumor development by 56% (P < 0.0001) and prolonging survival significantly (P < 0.0001) when compared to controls or CMF treated mice. The body weight of animals in the CSF-1 Fab and the CSF-1 Fab/CMF groups was significantly higher at the end of the survival studies compared to controls and CMF-treated animals (P < 0.0001). CSF-1 protein expression was abrogated in CSF-1 Fab-treated mice and significantly reduced in mice receiving combined CMF and anti-CSF-1 Fab treatment (P < 0.0001). CMF/Fab and Fab-treated mice had significantly reduced c-fms mRNA levels when compared to controls or CMF-treated mice (P < 0.0001). Combined treatment also reduced angiogenesis (P < 0.0001), decreased macrophage recruitment (P < 0.0001) and downregulated tumor matrix metalloprotease (MMP)-2, -9 and -12 expression (P < 0.0001). These studies support the paradigm of CSF-1 blockade in treatment of solid tumors and indicate that anti-CSF-1 antibodies are potent tools in breast cancer treatment. This study was supported by grant No. S9412-B11 from the Austrian Research Foundation to S. Aharinejad.

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Cancer Research: 66 (8 Supplement)
April 2006
Volume 66, Issue 8 Supplement
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CSF-1 antibody chemosensitizes human breast cancer in nude mice
Patrick Paulus, E. Richard Stanley and Seyedhossein Aharinejad
Cancer Res April 15 2006 (66) (8 Supplement) 575-576;

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CSF-1 antibody chemosensitizes human breast cancer in nude mice
Patrick Paulus, E. Richard Stanley and Seyedhossein Aharinejad
Cancer Res April 15 2006 (66) (8 Supplement) 575-576;
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Show more Experimental and Molecular Therapeutics 20: Advances in Cancer Therapeutics
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