Effective targeting of tumor vasculature by the angiogenesis inhibitors vasostatin and interleukin-12.
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-gamma (IFN-gamma) and the downstream chemokines interferon-inducible protein-10 (IP-10) and monokine induced by IFN-gamma. 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. (Blood. 2000;96:1900-1905)
Yao
L
L
Medicine Branch, National Cancer Institute, Division of Clinical Sciences, National Institutes of Health, Bethesda, MD 20892, USA.
Pike
S E
SE
Setsuda
J
J
Parekh
J
J
Gupta
G
G
Raffeld
M
M
Jaffe
E S
ES
Tosato
G
G
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002051:Burkitt Lymphoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D037282:Calreticulin; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018664:Interleukin-12 / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D010446:Peptide Fragments / Q000494:pharmacology*; D012261:Ribonucleoproteins / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D019394:Ki-67 Antigen; D010446:Peptide Fragments; D012261:Ribonucleoproteins; C121986:vasostatin; D018664:Interleukin-12