TRAIL is a potent inductor of apoptosis through activation of death receptors expressed on tumor cells. To improve the therapeutic activity of TRAIL, a novel tetravalent, bifunctional fusion protein was generated composed of single-chain Fv for targeted delivery (shown in blue), the IgE heavy chain domain 2 (EHD2) as covalently linked homodimerization module (shown in green), and a single-chain derivative of TRAIL as effector moiety (shown in red). Potent antitumoral effects were demonstrated for this scFv-EHD2-scTRAIL fusion protein in vitro and in vivo, further establishing the advantages of combining tumor targeting with dimeric presentation of scTRAIL. For details, see article by Seifert and colleagues on page 101.