A genetically encoded multifunctional TRAIL trimer facilitates cell-specific targeting and tumor cell killing.

ABSTRACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo2L) has been shown to exhibit potent and specific apoptotic activity against tumor cells. Several TRAIL constructs have been tried in patients, and the molecule remains under active clinical investigation. Native and recombinant TRAIL must form a homotrimer to become biologically active. However, noncovalently associated TRAIL displays a high degree of sensitivity to degradation, which limits its therapeutic potential. To enforce trimerization of the recombinant protein, we developed a covalently linked TRAIL trimer (TR3) by genetic fusion. This molecular drug design conferred improved stability without altering the native killing ability of TRAIL. Target specificity was shown by blocking TR3 activity with soluble death rec

SUBMITTER: Spitzer D 

PROVIDER: S-EPMC2947203 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature