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dc.contributor.authorMüller, Thomas R
dc.contributor.authorJarosch, Sebastian
dc.contributor.authorHammel, Monika
dc.contributor.authorLeube, Justin
dc.contributor.authorGrassmann, Simon
dc.contributor.authorBernard, Bettina
dc.contributor.authorEffenberger, Manuel
dc.contributor.authorAndrä, Immanuel
dc.contributor.authorChaudhry, M Zeeshan
dc.contributor.authorKäuferle, Theresa
dc.contributor.authorMalo, Antje
dc.contributor.authorCicin-Sain, Luka
dc.contributor.authorSteinberger, Peter
dc.contributor.authorFeuchtinger, Tobias
dc.contributor.authorProtzer, Ulrike
dc.contributor.authorSchumann, Kathrin
dc.contributor.authorNeuenhahn, Michael
dc.contributor.authorSchober, Kilian
dc.contributor.authorBusch, Dirk H
dc.date.accessioned2021-09-13T13:43:03Z
dc.date.available2021-09-13T13:43:03Z
dc.date.issued2021-08-17
dc.identifier.citationCell Rep Med. 2021 Aug 17;2(8):100374. doi: 10.1016/j.xcrm.2021.100374.en_US
dc.identifier.pmid34467251
dc.identifier.doi10.1016/j.xcrm.2021.100374
dc.identifier.urihttp://hdl.handle.net/10033/623026
dc.description.abstractAdoptive transfer of T cells expressing a transgenic T cell receptor (TCR) has the potential to revolutionize immunotherapy of infectious diseases and cancer. However, the generation of defined TCR-transgenic T cell medicinal products with predictable in vivo function still poses a major challenge and limits broader and more successful application of this "living drug." Here, by studying 51 different TCRs, we show that conventional genetic engineering by viral transduction leads to variable TCR expression and functionality as a result of variable transgene copy numbers and untargeted transgene integration. In contrast, CRISPR/Cas9-mediated TCR replacement enables defined, targeted TCR transgene insertion into the TCR gene locus. Thereby, T cell products display more homogeneous TCR expression similar to physiological T cells. Importantly, increased T cell product homogeneity after targeted TCR gene editing correlates with predictable in vivo T cell responses, which represents a crucial aspect for clinical application in adoptive T cell immunotherapy.en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectCRISPR/Cas9 mediated engineeringen_US
dc.subjectOTRen_US
dc.subjectT cell receptor engineeringen_US
dc.subjectTCRen_US
dc.subjectTCR editingen_US
dc.subjectTCR transgenic T cellsen_US
dc.subjecthomogenous TCR expreessionen_US
dc.subjectorthotopic TCR replacementen_US
dc.subjectpredictable functionalityen_US
dc.titleTargeted T cell receptor gene editing provides predictable T cell product function for immunotherapy.en_US
dc.typeArticleen_US
dc.identifier.eissn2666-3791
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalCell reports. Medicineen_US
dc.source.volume2
dc.source.issue8
dc.source.beginpage100374
dc.source.endpage
refterms.dateFOA2021-09-13T13:43:03Z
dc.source.journaltitleCell reports. Medicine
dc.source.countryUnited States


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Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International