Locoregional Apo2L/TRAIL eradicates intracranial human malignant glioma xenografts in athymic mice in the absence of neurotoxicity

Wilfried Roth, Stefan Isenmann, Ulrike Naumann, Sebastian Kügler, Mathias Bähr, Johannes Dichgans, Avi Ashkenazi, Michael Weller

    Research output: Contribution to journalArticle

    181 Scopus citations

    Abstract

    Glioblastoma multiforme is a lethal neoplasm refractory to radiochemotherapy. Although glioma cells undergo apoptosis when exposed to the death ligand, CD95 (Fas/APO-1) ligand, the therapeutic use of CD95L is considered impossible because of lethal side effects. Here, we report that the locoregional application of Apo2 ligand (Apo2L) exerts strong antitumor activity on preestablished intracraniably growing human U87MG glioma xenografts in athymic mice. Two repetitive intratumoral injections of 2 μg Apo2L resulted in long term survival of mice (> 100 days), whereas the median survival of mock-treated mice was 36 days. The assessment of tumor volumes at 21 and 35 days after inoculation showed complete eradication of glioma xenografts in Apo2L-treated mice. Histology and TUNEL assay confirmed the induction of apoptosis by Apo2L in glioma cells in vivo. Importantly, the intracerebral injection of Apo2L does not result in acute or delayed neurotoxicity. We propose that a phase 1 trial of intralesional Apo2L therapy for human glioblastoma multiforme is warranted.

    Original languageEnglish (US)
    Pages (from-to)479-483
    Number of pages5
    JournalBiochemical and biophysical research communications
    Volume265
    Issue number2
    DOIs
    StatePublished - Nov 19 1999

    Keywords

    • Apo2L (TRAIL)
    • Apoptosis
    • Death ligands
    • In vivo
    • Malignant glioma

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology

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