BOKU - Universität für Bodenkultur Wien - Forschungsinformationssystem

Gewählte Publikation:

Rodak, A; Stadlmayr, G; Stadlbauer, K; Lichtscheidl, D; Bobbili, MR; Rueker, F; Wozniak-Knopp, G.
(2021): Bispecific T-Cell Engagers Targeting Membrane-Bound IgE
BIOMEDICINES. 2021; 9(11), 1568 FullText FullText_BOKU

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 Fc epsilon RI 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-CD3 epsilon 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.
Autor*innen der BOKU Wien:
Rodak Aleksandra
Rüker Florian
Stadlbauer Katharina
Wozniak-Knopp Gordana
BOKU Gendermonitor:


Find related publications in this database (Keywords)
anti-IgE antibodies
bispecific T-cell engagers
cytotoxic T-lymphocyte mediated killing
extracellular membrane-proximal domain
Fc epsilon
T-cell activation


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