Potentiation of Antitumor Effect of Radiotherapy by Recombinant Tumor Necrosis Factor-α

Purpose : To determine whether TNF-α increases the antitumor effect of radiotherapy in murine syngeneic tumor system. Materials and Methods : Syngeneic murine tumors of MCa-K or MCa-4 (mammary carcinoma), OCa-I (ovarian carcinoma), or HCa-I(hepatocarcinoma were grown in hind legs of C3Hf/HeJ mice. When tumors were grown to 6 mm in mean diameter mice were treated with TNF-α, radiation, or combination of the both. Gamma-radiation was given as a single dose of 30 Gy for HCa-I and 15 Gy for other tumors using Cobalt-60 teletherapy unit. A novel TNF-α mutein developed in Korea, was intraperitoneally administered daily at a dose of 10 ug per mouse for 7 days. In combination of radiation and TNF-α, the drug was started 1 hour after radiation. Tumor growth delay assay was used to measure the tumor response to the treatment. Results : Among 4 tested tumors, TNF-α alone showed significant antitumor activity in MCa-K and OCa-I tumors, which showed absolute growth delay (AGD) of 5.0 days and 6.5 days, respectively. In combination with radiation, TNF-α showed significant delay of AGD (41.1 days) in OCA-I compared to AGDs of TNF-α alone and radiation, i.e., 6.5 days and 26.9 days, respectively(p