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Blood, 1 September 2000, Vol. 96, No. 5, pp. 1900-1905
NEOPLASIA
Effective targeting of tumor vasculature by the angiogenesis
inhibitors vasostatin and interleukin-12
Lei Yao,
Sandra E. Pike,
Joyce Setsuda,
Justin Parekh,
Ghanshyam Gupta,
Mark Raffeld,
Elaine S. Jaffe, and
Giovanna Tosato
From the Medicine Branch, National Cancer Institute,
Division of Clinical Sciences, National Institutes of Health, Bethesda,
MD; Center for Biologics Evaluation and Research, Rockville, MD; and
Laboratory of Pathology, National Cancer Institute, Division of
Clinical Science, National Institutes of Health, Bethesda, MD.
Solid tumors are dependent on preexisting vasculature and
neovascularization for their growth. Successful cancer therapies targeting the tumor vasculature would be expected to block the existing
tumor blood supply and to prevent tumor neovascularization. We tested
the antitumor activity of experimental therapy with 2 distinct
antiangiogenic drugs. Vasostatin inhibits endothelial cell growth and
neovascularization, and interleukin-12 (IL-12) targets the tumor
vasculature acting through interferon- (IFN-) and the downstream
chemokines interferon-inducible protein-10 (IP-10) and monokine induced
by IFN-. Individually, vasostatin and IL-12 produced distinct
efficacy profiles in trials aimed at reducing tumor growth in athymic
mice. In combination, these inhibitors halted the growth of human
Burkitt lymphoma, colon carcinoma, and ovarian carcinoma. Thus, cancer
therapy that combines distinct inhibitors of angiogenesis is a novel,
effective strategy for the experimental treatment of cancer.
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