Recombinant IgE antibody engineering to target EGFR

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

*Corresponding author for this work

Research output: Journal article (peer-reviewed)Journal article

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1565-1573
Number of pages9
JournalCancer Immunology, Immunotherapy
Volume61
Issue number9
DOIs
Publication statusPublished - Sept 2012
Externally publishedYes

Keywords

  • AllergoOncology symposium-in-writing
  • Antibody engineering
  • EGFR
  • Recombinant IgE
  • Tumor-targeting

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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