Abstracts (complete list) - Wissenschaft Online

Britta Schneider, Jeannette Gerspach, Sabine Münkel, Harald Wajant, Peter Scheurich,
Klaus Pfizenmaier
Novel TRAIL fusion proteins as promising candidates for
cancer therapy
Homotrimeric soluble TRAIL is currently been clinically exploited as cancer therapeutic,
but shows little antitumoral activity in monotherapy. In an attempt to further improve
TRAIL’s tumour selective activity we generated new TRAIL fusion proteins comprising an
antibody fragment (scFv) for targeting ErbB2. Further, a variant was designed, where
TRAIL is expressed as a single polypeptide chain (scTRAIL). Apoptotic activity of
scTRAIL is equivalent to a homotrimeric TRAIL molecule. We compared tumour
targeting and apoptosis induction of scTRAIL based and of conventional, homotrimeric
TRAIL fusion proteins with nontargeted TRAIL. Interestingly, among the tested TRAIL
molecules, the tumour antigen targeted scTRAIL fusion protein showed highest
apoptotic activity in vitro. The underlying mechanisms of this difference in apoptotic
activity will be discussed. Superior apoptosis induction of targeted TRAIL molecules
represent a promising strategy to improve TRAIL’s anti-tumoral action and minimizes
potential non-targeted actions on normal tissues.