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03.04.2020 | Laboratory Investigation

GD2 targeting by dinutuximab beta is a promising immunotherapeutic approach against malignant glioma

verfasst von: Sascha Marx, Fabian Wilken, Isabel Wagner, Madlen Marx, Sascha Troschke-Meurer, Maxi Zumpe, Sandra Bien-Moeller, Martin Weidemeier, Joerg Baldauf, Steffen K. Fleck, Bernhard H. Rauch, Henry W. S. Schroeder, Holger Lode, Nikolai Siebert

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2020

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Abstract

Purpose

Disialoganglioside GD₂ is expressed by glioblastoma multiforme (GBM) cells representing a promising target for anti-GD2 immunotherapeutic approaches. The aim of the present study was to investigate anti-tumor efficacy of the chimeric anti-GD₂ antibody (Ab) dinutuximab beta against GBM.

Methods

Expression levels of GD2 and complement regulatory proteins (CRP; CD46, CD55 and CD59) on well-known and newly established primary tumor originated GBM cell lines were analyzed by flow cytometry. Ab-dependent cellular (ADCC) and complement-dependent cytotoxicity (CDC) mediated by dinutuximab beta against GBM cells were determined by a non-radioactive calcein-AM-based assay.

Results

Analysis of primary GBM cells revealed a heterogeneous GD2 expression that varied between the cell lines analyzed with higher expression levels in the tumor surface compared to the core originated cells. Both GD2-positive and -negative tumor cells were detected in every cell line analyzed. In contrast to CDC, ADCC mediated by dinutuximab beta was observed against the majority of GBM cells. Importantly, CDC-resistant cells showed high expression of the CRP CD46, CD55 and CD59.

Conclusion

Our present data show anti-tumor effects mediated by dinutuximab beta against GBM cells providing a rationale for a GD2-directed immunotherapy against GBM. Due to high CRP expression, a combining of GD2-targeting with CRP blockade might be a further treatment option for GBM.

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Titel: GD2 targeting by dinutuximab beta is a promising immunotherapeutic approach against malignant glioma
verfasst von: Sascha Marx
Fabian Wilken
Isabel Wagner
Madlen Marx
Sascha Troschke-Meurer
Maxi Zumpe
Sandra Bien-Moeller
Martin Weidemeier
Joerg Baldauf
Steffen K. Fleck
Bernhard H. Rauch
Henry W. S. Schroeder
Holger Lode
Nikolai Siebert
Publikationsdatum: 03.04.2020
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 3/2020
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-020-03470-3

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GD2 targeting by dinutuximab beta is a promising immunotherapeutic approach against malignant glioma