Redirection of CAR-T Cell Cytotoxicity Using Metabolic Glycan Labeling with Unnatural Sugars

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dc.contributor.authorCha, Jeong Hyeonko
dc.contributor.authorKim, Eunsuko
dc.contributor.authorLee, Hyeong Jiko
dc.contributor.authorLee, Young-Hoko
dc.contributor.authorLee, Jeonghyunko
dc.contributor.authorKim, Eunhako
dc.contributor.authorKim, Chan Hyukko
dc.date.accessioned2023-12-05T07:00:26Z-
dc.date.available2023-12-05T07:00:26Z-
dc.date.created2023-07-03-
dc.date.issued2023-06-
dc.identifier.citationJOURNAL OF MEDICINAL CHEMISTRY, v.66, no.12, pp.7804 - 7812-
dc.identifier.issn0022-2623-
dc.identifier.urihttp://hdl.handle.net/10203/315731-
dc.description.abstractT cells expressing chimeric antigen receptors (CAR-Tcells) haveshown unprecedented clinical responses against hematological malignancies.However, some patients relapse after CAR-T cell therapy due to antigen-negativeescape variants. Additionally, CAR-T cell therapies showed limitedclinical efficacy in solid tumors with high antigen heterogeneity.To overcome this, we metabolically labeled the glycans on cancer cellsto redirect CAR-T cell cytotoxicity regardless of the endogenous antigenexpression status of the cancer cells. We found that modifying cancercells with N-azidoacetylmannosamine and bicyclo[6.1.0]non-4-yne-fluoresceinisothiocyanate can elicit selective and durable cytotoxicity of anti-FITCCAR-T cells. Furthermore, we demonstrated that dinitrophenyl-conjugatedsialic acid (Sia-DNP) generated DNP-modified glycans on cancer cellsin situ that could be effectively targeted by anti-DNP CAR-T cellsto eradicate established tumors in xenograft models. Our study illustratesthat metabolic glycan labeling using unnatural sugars can be combinedwith CAR-T cell therapy to provide novel cancer immunotherapy forsolid tumors that lack viable target antigens.-
dc.languageEnglish-
dc.publisherAMER CHEMICAL SOC-
dc.titleRedirection of CAR-T Cell Cytotoxicity Using Metabolic Glycan Labeling with Unnatural Sugars-
dc.typeArticle-
dc.identifier.wosid001010258900001-
dc.identifier.scopusid2-s2.0-85163492572-
dc.type.rimsART-
dc.citation.volume66-
dc.citation.issue12-
dc.citation.beginningpage7804-
dc.citation.endingpage7812-
dc.citation.publicationnameJOURNAL OF MEDICINAL CHEMISTRY-
dc.identifier.doi10.1021/acs.jmedchem.3c00048-
dc.contributor.localauthorKim, Chan Hyuk-
dc.contributor.nonIdAuthorKim, Eunsu-
dc.contributor.nonIdAuthorLee, Hyeong Ji-
dc.contributor.nonIdAuthorLee, Young-Ho-
dc.contributor.nonIdAuthorLee, Jeonghyun-
dc.contributor.nonIdAuthorKim, Eunha-
dc.description.isOpenAccessN-
dc.type.journalArticleArticle-
dc.subject.keywordPlusSIALIC-ACID-
dc.subject.keywordPlusIMMUNOTHERAPY-
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