INVITRO AND INVIVO ANTITUMOR-ACTIVITY OF RECOMBINANT MOUSE-TUMOR NECROSIS FACTOR (TNF) IN A MOUSE BLADDER-TUMOR (MBT-2)

Tumor necrosis factor (TNF) has confirmed anti-tumor activity. When used in combination with interferon gamma (IFNG) or chemotherapeutic drugs targeted at DNA topoisomerase II, synergistic cytotoxicity has been observed. Investigations of the anti-tumor activity of recombinant mouse TNF in a mouse bladder tumor model (MBT-2) were performed. The cytotoxicity of TNF and low dose actinomycin-D (AMD) against MBT-2 in vitro was examined alone and following preincubation with IFNG. The activity of TNF/AMD in vivo utilizing an intravesical implantation mode (MBT-2) was also evaluated. TNF alone had no cytotoxic effect in vitro TNF/AMD was cytotoxic for MBT-2 growth in vitro. Maximum cytotoxicity (86%) occurred at one μg./ml. TNF/one μg./ml. AMD with 50% cytotoxicity at .64 μg./ml. TNF/one/μg./ml. AMD. A two hour preincubation with IFNG markedly increased the cytotoxicity of TNF/AMD whereas longer incubations did not enhance cytotoxic activity. TNF alone and in combination with AMD did not significantly reduce the precentage of intravesical tumor outgrowth in vivo compared to controls. This study demonstrated that TNF/AMD exhibits cytotoxicity for MBT-2 cells in vitro but is ineffective in reducing implantation of intravesical tumors in vivo. The in vitro data suggest brief exposure of MBT-2 cells to IFNG augments the subsequent anti-tumor activity of TNF/AMD.