Effective targeting of tumor vasculature by the angiogenesis inhibitors vasostatin and interleukin-12

Solid tumors are dependent on preexisting vasculature and neovascularizatio n for their growth. Successful cancer therapies targeting the tumor vascula ture would be expected to block the existing tumor blood supply and to prev ent tumor neovascularization. We tested the antitumor activity of experimen tal therapy with 2 distinct antiangiogenic drugs. Vasostatin inhibits endot helial cell growth and neovascularization, and interleukin-12 (IL-12) targe ts the tumor vasculature acting through interferon-gamma (IFN-gamma) and th e downstream chemokines interferon-inducible protein-10 (IP-10) and monokin e induced by IFN-gamma. Individually, vasostatin and IL-12 produced distinc t efficacy profiles in trials aimed at reducing tumor growth in athymic mic e. In combination, these inhibitors halted the growth of human Burkitt lymp homa, colon carcinoma, and ovarian carcinoma. Thus, cancer therapy that com bines distinct inhibitors of angiogenesis is a novel, effective strategy fo r the experimental treatment of cancer. (C) 2000 by The American Society of Hematology.