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.
D000230:Adenocarcinoma / Q000628:therapy; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology / Q000627:therapeutic use*; D008545:Melanoma / Q000628:therapy*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000627:therapeutic use*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma