Bispecific T-Cell Engagers Targeting Membrane-Bound IgE

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 r...

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Autores principales:	Aleksandra Rodak, Gerhard Stadlmayr, Katharina Stadlbauer, Dominic Lichtscheidl, Madhusudhan Reddy Bobbili, Florian Rüker, Gordana Wozniak-Knopp
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	anti-IgE antibodies bispecific T-cell engagers cytotoxic T-lymphocyte mediated killing extracellular membrane-proximal domain Fcε T-cell activation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d5a2f8f936e9455eb7b76ffab63946c1
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id	oai:doaj.org-article:d5a2f8f936e9455eb7b76ffab63946c1
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spelling	oai:doaj.org-article:d5a2f8f936e9455eb7b76ffab63946c12021-11-25T16:49:07ZBispecific T-Cell Engagers Targeting Membrane-Bound IgE10.3390/biomedicines91115682227-9059https://doaj.org/article/d5a2f8f936e9455eb7b76ffab63946c12021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1568https://doaj.org/toc/2227-9059The 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.Aleksandra RodakGerhard StadlmayrKatharina StadlbauerDominic LichtscheidlMadhusudhan Reddy BobbiliFlorian RükerGordana Wozniak-KnoppMDPI AGarticleanti-IgE antibodiesbispecific T-cell engagerscytotoxic T-lymphocyte mediated killingextracellular membrane-proximal domainFcεT-cell activationBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1568, p 1568 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	anti-IgE antibodies bispecific T-cell engagers cytotoxic T-lymphocyte mediated killing extracellular membrane-proximal domain Fcε T-cell activation Biology (General) QH301-705.5
spellingShingle	anti-IgE antibodies bispecific T-cell engagers cytotoxic T-lymphocyte mediated killing extracellular membrane-proximal domain Fcε T-cell activation Biology (General) QH301-705.5 Aleksandra Rodak Gerhard Stadlmayr Katharina Stadlbauer Dominic Lichtscheidl Madhusudhan Reddy Bobbili Florian Rüker Gordana Wozniak-Knopp Bispecific T-Cell Engagers Targeting Membrane-Bound IgE
description	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.
format	article
author	Aleksandra Rodak Gerhard Stadlmayr Katharina Stadlbauer Dominic Lichtscheidl Madhusudhan Reddy Bobbili Florian Rüker Gordana Wozniak-Knopp
author_facet	Aleksandra Rodak Gerhard Stadlmayr Katharina Stadlbauer Dominic Lichtscheidl Madhusudhan Reddy Bobbili Florian Rüker Gordana Wozniak-Knopp
author_sort	Aleksandra Rodak
title	Bispecific T-Cell Engagers Targeting Membrane-Bound IgE
title_short	Bispecific T-Cell Engagers Targeting Membrane-Bound IgE
title_full	Bispecific T-Cell Engagers Targeting Membrane-Bound IgE
title_fullStr	Bispecific T-Cell Engagers Targeting Membrane-Bound IgE
title_full_unstemmed	Bispecific T-Cell Engagers Targeting Membrane-Bound IgE
title_sort	bispecific t-cell engagers targeting membrane-bound ige
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d5a2f8f936e9455eb7b76ffab63946c1
work_keys_str_mv	AT aleksandrarodak bispecifictcellengagerstargetingmembraneboundige AT gerhardstadlmayr bispecifictcellengagerstargetingmembraneboundige AT katharinastadlbauer bispecifictcellengagerstargetingmembraneboundige AT dominiclichtscheidl bispecifictcellengagerstargetingmembraneboundige AT madhusudhanreddybobbili bispecifictcellengagerstargetingmembraneboundige AT florianruker bispecifictcellengagerstargetingmembraneboundige AT gordanawozniakknopp bispecifictcellengagerstargetingmembraneboundige
_version_	1718412985221775360

Bispecific T-Cell Engagers Targeting Membrane-Bound IgE

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