Figure 3: Design of FasL/Fas-based cancer therapeutics. (a) Soluble homotrimeric FasL is essentially incapable of activating Fas-apoptotic signaling. However, hexamerized recombinant forms of sFasL have Fas-activating capacity analogous to membrane-expressed FasL. (b) The inactivity of homotrimeric sFasL has been exploited in scFv:FasL fusion proteins, by which the full apoptotic potential of FasL/Fas signaling is unleashed only upon target antigen-selective binding. To further increase the safety of FasL-based therapeutics, a FasL-based prodrug strategy analogous to TNF has been designed and evaluated.