The antitumor effect of intraperitoneal treatment with rhTNF-alpha muteinson Ehrlich ascites tumor growth

The intraperitoneal (i.p.) treatment with recombinant human tumor necrosis factor-alpha (rhTNF-alpha) is one of the possible therapies for tumors that are confined to the abdominal cavity. Clinical trials aiming at the exploi tation of the antitumor effects of rhTNF-alpha have been largely disappoint ing. In this model the activity of some rhTNF-alpha derivatives was studied . Ehrlich's ascites tumor (EAT) bearing Swiss albino male mice were treated i.p. three times a week with 10 mu g/mice of rhTNF-alpha, mutein Vor mutei n VI for two weeks, starting on the 4th day after tumor inoculation. Contro l mice received PBS. The effect of the rhTNF-alpha derivatives on the cours e of EAT was evaluated basing on: total ascites volume (TAV); packed cell v olume (PCV); total packed cell volume (TPCV); inhibitory growth rate (IGR); cellular population of EAT fluid; morphological EAT cell changes and mean survival time (MST). In the study mutein VI had only a slight effect on MST but significant on TAV- and TPCV-IGR (p< 0.001). In mice treated with rhTN F-alpha and mutein V the enhancement of MST (p<0.01) was accompanied by TAV - and TPCV-IGR (p<0.001). The number of EAT cells in ascites decreased afte r rhTNF-alpha and mutein V administration (p< 0.001). We conclude that trea tment with high-dose of this modified molecule lacking the possibility of b inding with p75R and not producing so intensified side effects is likely to find wider application in therapy and prevent the ascites growth just as r hTNF-alpha dosage.