The clinical success of the application of TNF-alpha in the setting of isolated limb perfusions in patients with advanced sarcomas, melanomas and other tumors has renewed the interest in TNF alpha as an anticancer drug in man. We have developed an interactive preclinical-clinical TNF alpha program that explores new methods to use TNF alpha in various settings or enhance its activity. Thus we have developed regional organ perfusion models and are testing the effectivity of targeting of TNF to the tumor by means systemic administration of long circulating liposomes. Furthermore various drugs and mechanisms that may enhance the activity of TNF alpha are under investigation. An overview of this comprehensive program is presented here.
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