Synergistic activity of tumor necrosis factor and interferon in a nude mouse model of human ovarian cancer.
In vitro and in vivo studies suggest a synergistic inhibition of tumor growth by the combination of certain interferons and tumor necrosis factors. We have examined the activity of two of these agents in an animal model of human ovarian cancer. The human ovarian cancer cell line SK-OV3 was grown subcutaneously in immunodeficient mice. Mean relative tumor volume was determined weekly by external tumor measurements and a standard formula. Animals were treated by intraperitoneal injection with (1) recombinant human tumor necrosis factor alpha (rHTNF) 5 or 10 micrograms/day; (2) recombinant murine interferon gamma (rMIFN) 5 x 10(4) units per day; or (3) a combination of rHTNF 5 micrograms/day and rMIFN 5 x 10(4) units/day. Simultaneous control groups were run for all experiments. Administration of rHTNF alone in either dose had no effect on rate of tumor growth. Administration of rMIFN at a dose of 5 x 10(4) units/day produced a marginal decrease in rate of tumor growth. Animals receiving both rHTNF 5 micrograms/day and rMIFN 5 x 10(4) units daily showed marked inhibition of tumor growth, with the mean relative tumor volume after 4 weeks of treatment measuring 0.75 +/- 0.91 in the treatment group and 11.06 +/- 2.96 in the control group. rHTNF and rMIFN demonstrate a synergistic inhibition of tumor growth in this animal model of human ovarian cancer.
Rubin
S C
SC
Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Hoskins
W J
WJ
Markman
M
M
Federici
M
M
Lloyd
K O
KO
Lewis
J L
JL
D000818:Animals; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma