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

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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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Acknowledgements

The authors thank Maria Asmus, Manuela Brueser and Theodor Koepp (University Medicine Greifswald, Pediatric Hematology and Oncology, Greifswald, Germany) for excellent technical assistance. We thank Marc Matthes for his help in preparing the illustrations.

Funding

Financial support was provided by the University Medicine Greifswald, Germany, the Gerhard-Domagk scholarship program, Germany, the Lieselotte-Beutel-Stiftung, Germany, the Forschungsverbund Molekulare Medizin Greifswald, Germany and Apeiron Biologics, Vienna, Austria.

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Authors and Affiliations

  1. Department of Neurosurgery, University Medicine Greifswald, 17475, Greifswald, Germany

    Sascha Marx, Fabian Wilken, Isabel Wagner, Sandra Bien-Moeller, Martin Weidemeier, Joerg Baldauf, Steffen K. Fleck & Henry W. S. Schroeder

  2. Department of Pediatric Oncology and Hematology, University Medicine Greifswald, 17475, Greifswald, Germany

    Fabian Wilken, Isabel Wagner, Madlen Marx, Sascha Troschke-Meurer, Maxi Zumpe, Holger Lode & Nikolai Siebert

  3. Department of Pharmacology, C_DAT, University Medicine Greifswald, 17475, Greifswald, Germany

    Sandra Bien-Moeller & Bernhard H. Rauch

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  1. Sascha Marx
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Correspondence to Sascha Marx.

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Marx, S., Wilken, F., Wagner, I. et al. GD2 targeting by dinutuximab beta is a promising immunotherapeutic approach against malignant glioma. J Neurooncol 147, 577–585 (2020). https://doi.org/10.1007/s11060-020-03470-3

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