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Synergistic Antitumor Effects of Rat -Interferon and Human Tumor Necrosis Factor against Androgen-dependent and -independent Rat Prostatic Tumors¹

Urological Research Laboratory, Department of Urology, University Hospital Nijmegen, P. O. Box 9101, 6500 HB Nijmegen [R. J. A. v. M., B. T. H., P. v. S., F. M. J. D., J. A. S.], and ITRI-TNO, Department of Immunomodulation, Rijswijk [P. H. v. d. M.], The Netherlands

We have examined the antitumor effects of rat -interferon (IFN-) and human tumor necrosis factor (TNF) against androgen-dependent and -independent Dunning rat prostatic tumors. In vitro studies, using the double layer soft agar assay, showed a very limited antiproliferative activity of the drugs in the dose range tested (1–1000 units IFN- and/or 1–1000 ng TNF/dish). For in vivo studies IFN- and TNF were administered s.c., peritumorally. IFN- was given 3 times/week, 8,000 or 80,000 units/rat, and TNF 5 times/week, 10 or 100 µg/rat. IFN- and TNF monotherapy were not significantly effective in inhibiting tumor growth, except for IFN- against the androgen-independent MatLyLu tumor. Combinations of IFN- and TNF had synergistic antiproliferative effects against all four tumor lines tested; however, complete growth inhibitions could not be achieved. Survival studies showed significant increase in survival of tumor-bearing rats.

¹ This work was supported in part by Grant KWF NUKC 8709/9001 from the Dutch Cancer Foundation.

² To whom requests for reprints should be addressed.

Received 10/30/90. Accepted 2/13/91.