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231226s2023 xx |||||o 00| ||eng c |
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|a 10.1016/j.clim.2023.109755
|2 doi
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|a pubmed24n1205.xml
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|a (DE-627)NLM36170870X
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|a (NLM)37673224
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|a (PII)S1521-6616(23)00518-1
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|a DE-627
|b ger
|c DE-627
|e rakwb
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| 041 |
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|a eng
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| 100 |
1 |
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|a Kim, Jun-Ho
|e verfasserin
|4 aut
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| 245 |
1 |
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|a Engineering bispecific T-cell engagers to deplete eosinophils for the treatment of severe eosinophilic asthma
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| 264 |
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|c 2023
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| 336 |
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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|a Date Completed 02.10.2023
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|a Date Revised 17.11.2023
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|a published: Print-Electronic
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|a ErratumIn: Clin Immunol. 2023 Dec;257:109841. - PMID 37977908
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|a Citation Status MEDLINE
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| 520 |
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|a Copyright © 2023 Elsevier Inc. All rights reserved.
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|a 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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4 |
|a Journal Article
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|a Research Support, Non-U.S. Gov't
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|a Bispecific T cell engager
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|a Eosinophils
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| 650 |
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|a IL-5 receptor alpha
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| 650 |
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|a Severe eosinophilic asthma
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| 650 |
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4 |
|a T-cell dependent cytotoxicity
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| 650 |
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|a Antibodies, Monoclonal
|2 NLM
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| 700 |
1 |
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|a Kim, Dae-Seong
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Park, Hae-Sim
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Kim, Yong-Sung
|e verfasserin
|4 aut
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| 773 |
0 |
8 |
|i Enthalten in
|t Clinical immunology (Orlando, Fla.)
|d 1999
|g 255(2023) vom: 01. Okt., Seite 109755
|w (DE-627)NLM098196855
|x 1521-7035
|7 nnns
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| 773 |
1 |
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|g volume:255
|g year:2023
|g day:01
|g month:10
|g pages:109755
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| 856 |
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|u http://dx.doi.org/10.1016/j.clim.2023.109755
|3 Volltext
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