Tumor necrosis factor as an adjunct to fractionated radiotherapy in the treatment of murine tumors.

Recombinant murine tumor necrosis factor (TNF) was investigated for its ability to increase the response of a murine mammary carcinoma to fractionated local tumor irradiation. When tumors in the leg of syngeneic mice grew to 8 mm in diameter (268 mm3), they were exposed to 3, 4 or 5 Gy gamma-rays daily for 10 days. Tumor necrosis factor was given 3 hr after each irradiation at a dose of 2 micrograms per mouse. Tumor growth delay was used as the endpoint. The effect of treatment with both agents combined was greater than the additive effect of the individual treatments. Tumor necrosis factor increased local tumor radiotherapy response by a factor of about 1.2, and by itself was effective in retarding the growth of both immunogenic and nonimmunogenic tumors. These experiments suggest that tumor necrosis factor in combination with radiotherapy may be beneficial for the treatment of cancer patients.