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Inhibition of angiogenesis and tumor growth by murine 7E3, the parent antibodyof c7E3 Fab (abciximab; ReoProTM)

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Abstract

Angiogenesis plays an essential role in the growth and dissemination of solid tumor cancers. The expression of endothelial cell integrin αvβ3 has been shown to increase during vascular proliferation associated with human tumors. Selective antagonists of αvβ3 can block angiogenesis and tumor growth by inducing programmed cell death in proliferating endothelial cells. Monoclonal antibody 7E3, an antagonist of the human, but not murine, integrins αvβ3 and αIIbβ3 (GPIIb/IIIa), inhibits platelet aggregation. It is the parent antibody of a mouse/human chimeric antibody fragment approved for adjunctive therapy of patients undergoing percutaneous coronary interventions to prevent ischemic complications (c7E3Fab; abciximab; ReoPro). To evaluate the potential of 7E3 to inhibit human angiogenesis and tumor growth independent of its antiplatelet effects, we established integrin αvβ3-negative human melanoma tumors in full-thickness human skin grafted onto SCID mice. The resulting tumors induce a human angiogenic response as assessed by the immunoreactivity of vascular cells with monoclonal antibodies specific for human CD31. Administration of 7E3 prevented or significantly inhibited the growth of tumors, and this effect correlated with a significant reduction in the number of blood vessels supplying the tumors. These results support the previous findings that blockade of integrin αvβ3 inhibits angiogenesis and tumor growth and indicates that dual inhibitors of αvβ3 and αIIbβ3 are effective in blocking tumor growth and angiogenesis.

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Authors and Affiliations

  1. Department of Medicine, Cellular and Molecular Medicine East 3050, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0684, USA

    Judith A. Varner

  2. Centocor, Inc., 200 Great Valley Parkway, Malvern, PA, 19355-1307, USA

    Marian T. Nakada & Robert E. Jordan

  3. Department of Medicine, Mt. Sinai Medical Center, Box 1118, 1 Gustave L. Levy Place, New York, NY, 10029-6575, USA

    Barry S. Coller

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  1. Judith A. Varner
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  2. Marian T. Nakada
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  3. Robert E. Jordan
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  4. Barry S. Coller
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Varner, J.A., Nakada, M.T., Jordan, R.E. et al. Inhibition of angiogenesis and tumor growth by murine 7E3, the parent antibodyof c7E3 Fab (abciximab; ReoProTM). Angiogenesis 3, 53–60 (1999). https://doi.org/10.1023/A:1009019223744

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