“…CD95, so-called Fas or Apo1, is the best-known death receptor belonging to the TNF receptor superfamily (Schmitz et al, 2000;Timmer et al, 2002); however, before long it was appreciated that systemic treatment with Fas-targeting therapy causes severe liver damage (Ogasawara et al, 1993;Galle et al, 1995). The therapeutic potential of TNFa was also tempered by the demonstration that the systemic administration of recombinant TNFa resulted in a significant systemic toxicity associated with its strong pro-inflammatory activity, including fever, lung or liver failure, increased blood clotting and hypotension (Creaven et al, 1987;Creagen et al, 1988;Hersh et al, 1991;Vassalli, 1992). Thus, the use of Fas or TNFa receptors as cancer targets appeared fruitless, and more recently efforts have been made to focus on minimizing unfavorable side effects by using local administration, inducible FasL-or TNF-expressing vectors, and tumor targeting gene delivery methods (Kircheis et al, 2002).…”