Combination antitumor therapy with rabbit tumor necrosis factor and chemo- and immuno-therapeutic agents against murine tumors.

The antitumor activity of partially purified rabbit tumor necrosis factor (TNF) in combination with lentinan or chemotherapeutic agents was tested. Partially purified TNF was obtained from TNF-containing rabbit sera by salt precipitation and ion-exchange chromatography. Its specific activity, determined in vitro as its cytotoxic activity against L929 cells in the presence of actinomycin D, was 10(5) U/mg protein or about 30-fold that of the crude rabbit sera. The growths of MH134 hepatoma in C3H/He mice and Lewis lung carcinoma in C57BL/6 mice were partially inhibited by intratumoral administration of a suboptimal dose of the TNF preparation. Additional treatment with lentinan, actinomycin D, mitomycin C or adriamycin significantly increased the antitumor activity. In particular, combination therapy with TNF and lentinan was very effective against MH134 hepatoma without having detectable side-effects, showing that lentinan expanded the therapeutical potential of TNF. These results are discussed in relation to our previous results on combination antitumor therapy.