Effects of Tumor Necrosis Factor and Hyperthermia on Meth‐A Tumors

The combined effects of purified human natural tumor necrosis factor (TNF) and hyperthermia were investigated in a transplanted TNF‐sensitive Meth‐A tumor model. We assessed the sequence and interval for the two treatments, the temperature that caused maximal heat sensitization, and the effects of pH modification on this combination therapy. Tumor response was evaluated by means of a tumor growth delay assay. TNF at a dose of 50 JRU/g caused significant tumor growth delay. A synergistic effect of TNF and hyperthermia was observed when TNF was administered 10 min before heating. This thermal enhancement of the action of TNF became more prominent with an increase in the heating temperature. Tumor growth delay was maximal when TNF was given immediately before or after hyperthermia. However, after an increase in the time interval to more than 2 h, there was no enhancement of growth delay. Injection of glucose (5 g/kg) caused a significant fall in pH at 10 and 30 min after administration. Further enhancement in tumor growth delay was seen with the tri‐modality of glucose, TNF, and heat compared to combined treatment with heat and either TNF or glucose at a hyperthermia of 42°C. This effect was not obtained with heating to 40°C. TNF appears to be a potent heat sensitizer when an appropriate temperature and time interval between hyperthermia and TNF administration are used. Trimodality treatment with hyperthermia, TNF, and glucose may be a new method of anticancer therapy.