Synergistic antitumour effect of TNF-SAM2 with melphalan and doxorubicin in isolated limb perfusion in rats

An isolated limb perfusion model (ILP) using soft tissue sarcoma bearing ra ts (BN175) was used to study antitumour activity of a tumour necrosis facto r alpha mutant (TNF-SAM2) in combination with melphalan and doxorubicin. Pr ogressive disease was demonstrated after ILP without agents (sham) or with 50 mug TNF-SAM2. ILP with 40 mug melphalan or 400 mug doxorubicin resulted in no change of tumour volume of progressive disease five days after perfus ion. Partial and complete response rates were demonstrated in 76% of rats w izen the combination of TNF-SAM2 and melphalan was used. TNF-SAM2 in combin ation with doxorubicin was synergistic as well with a 70% response I ate. H istopathologically, these responses consisted of hemorrhagic necrosis of th e coagulative type. 2 In conclusion, TNF-SAM2 has similar antitumour activi ty in combination with melphalan ol doxorubicin as rHuTNF in sarcoma-bearin g mts and is eligible to be rested in clinical ILP or ol gan perfusion sett ings because of its potential decreased toxicity.