Engineering bispecific T-cell engagers to deplete eosinophils for the treatment of severe eosinophilic asthma
Copyright © 2023 Elsevier Inc. All rights reserved.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 255(2023) vom: 01. Okt., Seite 109755 |
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| Weitere Verfasser: | , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2023
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Bispecific T cell engager Eosinophils IL-5 receptor alpha Severe eosinophilic asthma T-cell dependent cytotoxicity Antibodies, Monoclonal |
| Zusammenfassung: | Copyright © 2023 Elsevier Inc. All rights reserved. Severe eosinophilic asthma (SEA) is characterized by elevated eosinophil counts in the blood and airway mucosa. While monoclonal antibody therapies targeting interleukin-5 (IL-5) and its receptor (IL-5Rα) have improved treatment, some patients remain unresponsive. We propose an alternative approach to eliminate eosinophils using T cells by engineering IL-5Rα × CD3 bispecific T-cell engagers (bsTCEs) that target both IL-5Rα on eosinophils and CD3 on T cells. We designed different formats of IL-5Rα × CD3 bsTCEs, incorporating variations in valency, geometry, and affinity for the target antigen binding. We identified the single-chain variable fragment (scFv)-Fc format with the highest affinity toward the membrane-proximal domain of IL-5Rα in the IL-5Rα-binding arm showed the most potent cytotoxicity against IL-5Rα-expressing peripheral eosinophils by activating autologous primary T cells from healthy donors. This study proposes IL-5Rα × CD3 bsTCEs as potential alternatives for SEA treatment. Importantly, it demonstrates the first application of bsTCEs in eliminating disease-associated cells, including eosinophils, beyond cancer cells |
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| Beschreibung: | Date Completed 02.10.2023 Date Revised 17.11.2023 published: Print-Electronic ErratumIn: Clin Immunol. 2023 Dec;257:109841. - PMID 37977908 Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2023.109755 |