1988 Volume 79 Issue 10 Pages 1613-1621
In order to examine the effect of human recombinant tumor necrosis factor (rHu-TNF) given alone or in combination with human lymphoblastoid interferon (HLBI) against renal cell carcinoma, a sensitivity test was done using xenografts of human renal cell carcinoma serially transplanted in nude mice (AM-RC-3).
The dosages of the drugs used were as follows, rHu-TNF alone was administered daily for 7 days in a dose of 1, 000U, 3, 000U or 10, 000U by either the intra-tumoral or the intravenous route. In the case of combined therapy, rHu-TNF (1, 000U, 3, 000U, or 10, 000U i. t.) and HLBI (107U/kg i. p.) were injected daily for seven days.
The therapeutic effects were evaluated according to the criteria of Battelle Columbus (i. e., relative mean tumor weight (RW) and T/C ratio of RW (TRW/CRW), and the histopathological changes were observed.
Based on the RW, only the group that received intra-tumoral rHu-TNF (10, 000U) showed tumor regression (RW=0.65). In terms of TRW/CRW, marked retardation in tumor growth was seen in the group that received rHu-TNF (10, 000U) alone by intra-tumoral injection (15.3%), or after combination therapy with rHu-TNF (3, 000U or 10, 000U) and HLBI (107U/kg) (27.8% and 39.7%, respectively).
A strong inhibitory effect on tumor growth was recognized in the order of 10, 000U, 3, 000U and 1, 000U after intra-tumoral administration of rHu-TNF alone. This suggests that rHu-TNF exhibits its anti-tumor effect against AM-RC-3 in a dose-dependent manner.
Investigation of the RW and TRW/CRW after intra-tumoral administration and after intravenous injection showed the former route of administration to be more effective than the latter.
As compared to treatment with rHu-TNF alone, combined therapy with HLBI showed a significantly enhanced anti-tumor effect only at a dose of 3, 000U of rHu-TNF.
Histopathologically, remarkable coagulation necrosis of tumor cells accompanied by hemorrhage was demonstrated in the following group: rHu-TNF 3, 000U (i. t.), 10, 000U (i. t.), rHu-TNF 3, 000U (i. t.) plus HLBI 107U/kg and rHu-TNF 10, 000U (i. t.) plus HLBI 107U/kg.
