TNF and some of its brethren, including FasL (CD95L) and Lta, function normally as powerful mediators and regulators of immune responses in vivo. However, when administered at pharmacologic doses, they caused extreme hepatotoxicity, which prevented their general use as cancer therapeutics. Still, those discoveries touched off a major effort to find similarly active molecules with lower toxicity, and in the mid-1990s, researchers at Immunex and Genentech, Inc. of San Francisco, Calif., independently discovered just such a molecule, the TNF-related apoptosis-inducing ligand (TRAIL).3,4
Recently, the two companies agreed to co-develop this molecule (now known as TRAIL/Apo-2L) for the treatment of cancer.
The trouble with TRAIL/Apo-2L is that, as a Type II transmembrane protein, it does not adopt the biologically active trimer conformation outside the cell membrane. In the Hot Paper published by Lynch and his colleagues at Immunex, the authors reported creating a soluble form of the trimer by using an ...
