SYNERGISTIC CYTO-TOXIC AND ANTITUMOR EFFECTS OF RECOMBINANT HUMAN-TUMOR NECROSIS FACTOR AND HYPERTHERMIA

  • 1 February 1988
    • journal article
    • research article
    • Vol. 48  (3) , 650-653
Abstract
A synergistic increase in the cytotoxic effects of recombinant human tumor necrosis factor (rH-TNF) and hyperthermia was demonstrated both in vitro and in vivo. The cytotoxicity of rH-TNF against L-M cells in incubation for 12 h at 38.5 and 40.degree. C based on the concentration necessary for 50% cytotoxicity was, respectively, 125 and more than 500 times as high as in similar incubation at 37.degree. C. As observed 18 days after implantation of Meth-A fibrosarcoma cells in mice, single i.v. administration of rH-TNF at 1000 units/mouse resulted in complete cures in five mice when performed in combination with hyperthermia (40.degree. C), whereas rH-TNF alone in the same dose resulted in 27.1% inhibition of tumor growth and hyperthermia alone had no appreciable effect on tumor growth. The i.v. administration of rH-TNF three times at 100 or 300 units/mouse together with hyperthermia (40.degree. C) resulted in 41.2 and 89.0% tumor growth inhibition, respectively; similar administration without hyperthermia appeared to have little or no appreciable effect on tumor growth. The result suggest that combination therapy including rH-TNF and hyperthermia may be of value in the treatment of malignancy in human patients.