Erschienen in:
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
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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.