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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 9/2012

01-09-2012 | Symposium-in-writing paper

Recombinant IgE antibody engineering to target EGFR

Authors: Edzard Spillner, Melanie Plum, Simon Blank, Michaela Miehe, Josef Singer, Ingke Braren

Published in: Cancer Immunology, Immunotherapy | Issue 9/2012

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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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Metadata
Title
Recombinant IgE antibody engineering to target EGFR
Authors
Edzard Spillner
Melanie Plum
Simon Blank
Michaela Miehe
Josef Singer
Ingke Braren
Publication date
01-09-2012
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 9/2012
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-012-1287-4

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