Death receptor targeting has emerged as one of the promising novel approaches of
cancer therapy. The activation of one such prototypic
death receptor, CD95 (Fas/APO-1), has remained controversial because CD95 agonistic molecules have exhibited either too strong toxicity or too little activity. The natural
CD95 ligand (
CD95L) is a
cytokine, which needs to trimerize to mediate a cell death signal.
Mega-Fas-Ligand, now referred to as APO010, is a synthetic hexameric CD95 agonist that exhibits strong antitumor activity in various
tumor models. Here, we studied the effects of APO010 in human
glioma models in vitro and in vivo. Compared with a cross-linked soluble
CD95L or a CD95-agonistic antibody, APO010 exhibited superior activity in
glioma cell lines expressing CD95 and triggered
caspase-dependent cell death. APO010 reduced
glioma cell viability in synergy when combined with
temozolomide. The locoregional administration of APO010 induced
glioma cell death in vivo and prolonged the survival of
tumor-bearing mice. A further exploration of APO010 as a novel antiglioma agent is warranted.