Potentiated antitumor effects of interleukin 12 and matrix metalloproteinase inhibitor batimastat against B16F10 melanoma in mice.
The application of antiangiogenic agents in cancer therapy has been studied extensively. Combination of agents with antiangiogenic properties could possibly enhance antitumor effects. Interleukin 12 is a cytokine with potent antitumor activity mediated also via antiangiogenic mechanisms. These effects are attributed to IFN-gamma production stimulated by IL-12. Since IFN-gamma has been reported to augment antitumor effects when combined with one of the metalloproteinase inhibitors--batimastat (BB-94), we have examined a combined treatment with IL-12 and BB-94 in a murine melanoma model. The administration of both agents showed potentiated antitumor activity. Furthermore, we have shown in a tumor-induced angiogenesis model that the combined application of IL-12 and batimastat inhibits the formation of new blood vessels to a greater extent than either agent alone. Our observations show that antiangiogenic effects are at least partly responsible for the enhanced antitumor effects of the combined treatment with IL-12 and BB-94.
Dabrowska
A
A
Department of Immunology, Medical University of Warsaw, Poland.
Giermasz
A
A
Marczak
M
M
Gołab
J
J
Jakóbisiak
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004357:Drug Synergism; D018664:Interleukin-12 / Q000494:pharmacology / Q000627:therapeutic use*; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000276:Adjuvants, Immunologic; D020533:Angiogenesis Inhibitors; D009363:Neoplasm Proteins; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D013876:Thiophenes; D018664:Interleukin-12; D010649:Phenylalanine; C080985:batimastat; D008666:Metalloendopeptidases