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Recombinant IgE antibody engineering to target EGFR

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Abstract

Monoclonal antibodies have become a mainstay for the targeted treatment of cancer today. Some of the most successful targets of monoclonal antibodies are constituted by the epidermal growth factor receptor family spearheaded by the epidermal growth factor receptor (EGFR). Prompted by studies indicating that IgE compared to IgG may harness alternate effector functions to eradicate malignant cells, we addressed the establishment, engineering, and the potential tumoricidal effects of recombinant anti-EGFR IgE. Therefore, two different therapeutic EGFR-specific antibodies, 225 and 425, were chosen for re-cloning into different chimeric IgE and IgG formats and produced in human cells. Simultaneous antibody binding to the sEGFR demonstrated accessibility of both epitopes for recombinant IgE. Proliferation and cytotoxicity assays demonstrated signal blocking and effector mediating capability of IgE isotypes. Pronounced degranulation in the presence of sEGFR upon activation exclusively with two IgE antibodies verified the epitope proximity and provides evidence that tumor-targeting by anti-EGFR IgE is safe with regard to soluble target structures. Degranulation mediated by tumor cells expressing EGFR could be demonstrated for singular and combined IgE antibodies; however, use of two IgE specificities was not superior to use of one IgE alone. The data suggest that the surface distribution of EGFR is optimally suited to mount a robust effector cell trigger and corroborate the potential and specificity of the IgE/IgE receptor network to react to xenobiotic or pathogenic patterns for targeting malignancies.

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Acknowledgments

The authors would like to thank Dr. Kerstin Greunke for helpful discussions and critical reading of the manuscript. JS was supported by Austrian Science Fund projects P 23398-B11 and W1205-B09 (doctoral college CCHD).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Chemistry, Institute of Biochemistry and Molecular Biology, University of Hamburg, Martin-Luther-King-Platz 6, 20146, Hamburg, Germany

    Edzard Spillner, Melanie Plum & Simon Blank

  2. Hamburg Center for Experimental Therapy Research (HEXT), University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Michaela Miehe & Ingke Braren

  3. Comparative Medicine, Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University Vienna, University Vienna, Vienna, Austria

    Josef Singer

  4. Comparative Immunology & Oncology, Institute for Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University Vienna, University of Vienna, Vienna, Austria

    Josef Singer

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  1. Edzard Spillner
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  2. Melanie Plum
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  4. Michaela Miehe
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Correspondence to Edzard Spillner.

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This paper is part of the Symposium in Writing: AllergoOncology, the role of Th2 responses in cancer.

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Spillner, E., Plum, M., Blank, S. et al. Recombinant IgE antibody engineering to target EGFR. Cancer Immunol Immunother 61, 1565–1573 (2012). https://doi.org/10.1007/s00262-012-1287-4

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