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APO010, a synthetic hexameric CD95 ligand, induces human glioma cell death in vitro and in vivo


Eisele, G; Roth, P; Hasenbach, K; Aulwurm, S; Wolpert, F; Tabatabai, G; Wick, W; Weller, M (2011). APO010, a synthetic hexameric CD95 ligand, induces human glioma cell death in vitro and in vivo. Neuro-Oncology, 13(2):155-164.

Abstract

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Date:2 February 2011
Deposited On:12 Mar 2011 08:55
Last Modified:05 Apr 2016 14:37
Publisher:Oxford University Press
ISSN:1522-8517
Additional Information:This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Neuro-Oncology following peer review. The definitive publisher-authenticated version Neuro Oncol (2011) 13(2): 155-164 first published online December 22, 2010 doi:10.1093/neuonc/noq176 is available online at: http://neuro-oncology.oxfordjournals.org/content/13/2.toc
Publisher DOI:10.1093/neuonc/noq176
PubMed ID:21183510
Permanent URL: http://doi.org/10.5167/uzh-43014

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