The in vitro antitumor activity of recombinant alpha- and gamma-Interferon as well as recombinant Tumor Necrosis Factor alpha was tested on renal cell carcinoma xenografts using the double layer soft agar method. Using this assay, the effect of the drugs on the clonogenic potential of tumor cells in soft agar was determined and used as an indication for the antiproliferative capacity of these drugs. There appeared to be a differential response of the tested xenografts towards these drugs in a dose dependent way. However, when used in combination in most cases an additive or synergistic effect was observed. Even though again the response was differential, the combination of alpha-Interferon (10 ng/dish) and Tumor Necrosis Factor (100 ng/dish) resulted in a complete inhibition of colony formation in soft agar for both tumor lines. We conclude that there is a direct effect of alpha-Interferon, gamma-Interferon and Tumor Necrosis Factor on renal cell carcinoma xenografts. In combination drug tests the effect of alpha-Interferon and Tumor Necrosis Factor was strongly synergistic. The implication of these studies for in vivo use of these drugs remain to be established.

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The in vitro antitumor activity of alpha- and gamma-interferon as well as tumor necrosis factor was tested on two human renal cell carcinoma xenografts--RC-43 and NC-65. A dose-dependent inhibition of colony formation in soft agar was found for both tumor lines. NC-65, however, showed no sensitivity for gamma-interferon. Combination drug tests showed a synergistic effect on colony formation of both tumor lines. The strongest inhibition was shown by the combination of alpha-interferon and tumor necrosis factor. We conclude that both interferons as well as tumor necrosis factor show direct in vitro cytostatic effects against renal tumor direct in vitro cytostatic effects against renal tumor cells.