Tumor necrosis factor-alpha in isolated perfusion systems in the treatment of cancer: The Rotterdam preclinical-clinical program

The clinical success of the application of tumor necrosis factor-α (TNFα) in isolated limb perfusions in patients with advanced sarcomas, melanomas and other tumors has renewed the interest in this agent as an anticancer drug. At the Rotterdam Cancer Center, we have developed an interactive preclinical-clinical TNFα program that explores new methods to use TNFα in various settings. Regional organ perfusion models were developed and the effectivity of targeting of TNFα to the tumor by means of systemic administration of liposomes are tested. Furthermore various drugs and mechanisms that may enhance the activity of TNFα ate under investigation. A summary of this comprehensive program is presented here.