Synergistic enhancement of the antitumor activity of recombinant human TNF-alpha by recombinant human IFN-gamma.

The effect of recombinant human interferon-gamma (rHu-IFN-gamma) on the antitumor activity of recombinant human tumor necrosis factor (rHu-TNF-alpha) was examined in vitro and in vivo. rHu-IFN-gamma enhanced both cytostatic and cytocidal activity of rHu-TNF-alpha against most rHu-TNF-alpha-sensitive tumor cells in vitro. However, there was no correlation between the degree of enhancement by rHu-IFN-gamma and that of the susceptibility of tumor cells to rHu-TNF-alpha. The enhancing effect of rHu-IFN-gamma was most marked when tumor cells were treated with rHu-IFN-gamma either for 1 day before treatment with rHu-TNF-alpha or for the first day of the exposure to rHu-TNF-alpha. A marked enhancing effect of rHu-IFN-gamma was also observed in the in vivo antitumor activity of rHu-TNF-alpha against HMV-2 melanoma. A combined treatment with rHu-TNF-alpha and rHu-IFN-gamma in a patient with papillary adenocarcinomas was shown to be much more effective than treatment with rHu-TNF-alpha alone. These results suggest that combined treatment with both agents will have better results in clinical trials.