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Engineering bispecific T-cell engagers to deplete eosinophils for the treatment of severe eosinophilic asthma

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dc.contributor.authorKim, JH-
dc.contributor.authorKim, DS-
dc.contributor.authorPark, HS-
dc.contributor.authorKim, YS-
dc.date.accessioned2023-10-24T07:46:23Z-
dc.date.available2023-10-24T07:46:23Z-
dc.date.issued2023-
dc.identifier.issn1521-6616-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/26442-
dc.description.abstractSevere 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.-
dc.language.isoen-
dc.subject.MESHAntibodies, Monoclonal-
dc.subject.MESHAsthma-
dc.subject.MESHEosinophils-
dc.subject.MESHHumans-
dc.subject.MESHT-Lymphocytes-
dc.titleEngineering bispecific T-cell engagers to deplete eosinophils for the treatment of severe eosinophilic asthma-
dc.typeArticle-
dc.identifier.pmid37673224-
dc.subject.keywordBispecific T cell engager-
dc.subject.keywordEosinophils-
dc.subject.keywordIL-5 receptor alpha-
dc.subject.keywordSevere eosinophilic asthma-
dc.subject.keywordT-cell dependent cytotoxicity-
dc.contributor.affiliatedAuthorPark, HS-
dc.type.localJournal Papers-
dc.identifier.doi10.1016/j.clim.2023.109755-
dc.citation.titleClinical immunology (Orlando, Fla.)-
dc.citation.volume255-
dc.citation.date2023-
dc.citation.startPage109755-
dc.citation.endPage109755-
dc.identifier.bibliographicCitationClinical immunology (Orlando, Fla.), 255. : 109755-109755, 2023-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissn1521-7035-
dc.relation.journalidJ015216616-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
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