Bispecific T-Cell Engagers Targeting Membrane-Bound IgE

Institute of Molecular Biotechnology, Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna (BOKU), Muthgasse 18, 1190 Vienna, Austria

Ludwig Boltzmann Institute for Experimental, Clinical Traumatology in the AUVA Research Center, Donaueschingenstrasse 13, 1200 Vienna, Austria

Author to whom correspondence should be addressed.

Academic Editor: Daniel López

Biomedicines 2021, 9(11), 1568; https://doi.org/10.3390/biomedicines9111568

Received: 12 September 2021 / Revised: 7 October 2021 / Accepted: 26 October 2021 / Published: 29 October 2021

(This article belongs to the Special Issue Immunoglobulins in Inflammation 2.0)

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Abstract

The increased incidence of allergies and asthma has sparked interest in IgE, the central player in the allergic response. Interaction with its high-affinity receptor FcεRI leads to sensitization and allergen presentation, extracellular membrane-proximal domain in membrane IgE can act as an antigen receptor on B cells, and the interaction with low-affinity IgE receptor CD23 additionally influences its homeostatic range. Therapeutic anti-IgE antibodies act by the inhibition of IgE functions by interfering with its receptor binding or by the obliteration of IgE-B cells, causing a reduction of serum IgE levels. Fusion proteins of antibody fragments that can act as bispecific T-cell engagers have proven very potent in eliciting cytotoxic T-lymphocyte-mediated killing. We have tested five anti-IgE Fc antibodies, recognizing different epitopes on the membrane-expressed IgE, for the ability to elicit specific T-cell activation when expressed as single-chain Fv fragments fused with anti-CD3ε single-chain antibody. All candidates could specifically stain the cell line, expressing the membrane-bound IgE-Fc and bind to CD3-positive Jurkat cells, and the specific activation of engineered CD3-overexpressing Jurkat cells and non-stimulated CD8-positive cells was demonstrated for 8D6- and ligelizumab-based bispecific antibodies. Thus, such anti-IgE antibodies have the potential to be developed into agents that reduce the serum IgE concentration by lowering the numbers of IgE-secreting cells. View Full-Text

Keywords: anti-IgE antibodies; bispecific T-cell engagers; cytotoxic T-lymphocyte mediated killing; extracellular membrane-proximal domain; Fcε; T-cell activation

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MDPI and ACS Style

Rodak, A.; Stadlmayr, G.; Stadlbauer, K.; Lichtscheidl, D.; Bobbili, M.R.; Rüker, F.; Wozniak-Knopp, G. Bispecific T-Cell Engagers Targeting Membrane-Bound IgE. Biomedicines 2021, 9, 1568. https://doi.org/10.3390/biomedicines9111568

AMA Style

Rodak A, Stadlmayr G, Stadlbauer K, Lichtscheidl D, Bobbili MR, Rüker F, Wozniak-Knopp G. Bispecific T-Cell Engagers Targeting Membrane-Bound IgE. Biomedicines. 2021; 9(11):1568. https://doi.org/10.3390/biomedicines9111568

Chicago/Turabian Style

Rodak, Aleksandra, Gerhard Stadlmayr, Katharina Stadlbauer, Dominic Lichtscheidl, Madhusudhan Reddy Bobbili, Florian Rüker, and Gordana Wozniak-Knopp. 2021. "Bispecific T-Cell Engagers Targeting Membrane-Bound IgE" Biomedicines 9, no. 11: 1568. https://doi.org/10.3390/biomedicines9111568

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