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The Designed Angiostatic Peptide Anginex Synergistically Improves Chemotherapy and Antiangiogenesis Therapy with Angiostatin¹

Departments of Biochemistry [R. P. M. D., K. H. M.] and Pharmacology [Y. Y., S. R.], University of Minnesota Health Sciences Center, Minneapolis, Minnesota 55455, and Tumor Angiogenesis Laboratory, Department of Internal Medicine, University Hospital Maastricht, 6202 AZ Maastricht, the Netherlands [R. P. M. D., A. W. G.]

Recently, we demonstrated that the designed peptide anginex displays potent antiangiogenic activity. The aim of the present study was to investigate anginex treatment as a single-agent therapy and to test its ability to improve conventional chemotherapy and antiangiogenesis therapy. In a human ovarian carcinoma mouse model, anginex inhibited tumor growth by 70%. When anginex was combined with a suboptimal dose of carboplatin, tumors regressed to an impalpable state. Anginex plus angiostatin worked synergistically to inhibit tumor growth. Assessment of microvessel density suggested that the antitumor activity of anginex is mediated by angiogenesis inhibition. In any of the experiments, no sign of anginex-induced toxicity was observed.

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