Study on the Synergistic Effects of Recombinant Human TNF and Hyperthermia

It was attempted to increase the anti-tumor activity of recombinant human tumor necrosis factor (rH-TNF) by combining it with hyperthermia in vitro and in two murine models. L-M cells were incubated with rH-TNF (1?10000JRU/ml) at 38.5℃ or 40℃ for 1 hr, 6 hrs and 12 hrs. Cytotoxicity was not enhanced more than that obtained under incubation at 37℃ for 1 hr, but a synergistic effect was observed after 6 hrs and 12 hrs. An apparent, though not significant, synergism of hyperthermia (40℃ 30 min, 3 times) and rH-TNF (100 JRU/mouse, 3 times) was found against subcutaneously inoculated Meth-A tumors in BALB/c mice. The synergism with hyperthermia (40℃ 30 min) became significant at dosages of rH-TNF of 300 JRU/mouse (three administrations) or 1000 JRU/mouse. Necrotic change of the inoculated Meth-A tumors caused by rH-TNF was also enhanced by hyperthermia. The synergistic effect was further confirmed in an artificial metastasis model. The number of metastatic nodules on the surface of lung from the mouse inoculated with Meth-A F15 cells was significantly (p