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dc.contributor.authorSheih, Alyssaen_US
dc.contributor.authorVoillet, Valentinen_US
dc.contributor.authorHanafi, Laïla-Aïchaen_US
dc.contributor.authorDeBerg, Hannah A.en_US
dc.contributor.authorYajima, Masanaoen_US
dc.contributor.authorHawkins, Reeden_US
dc.contributor.authorGersuk, Vivianen_US
dc.contributor.authorRiddell, Stanley R.en_US
dc.contributor.authorMaloney, David G.en_US
dc.contributor.authorWohlfahrt, Martin E.en_US
dc.contributor.authorPande, Dnyanadaen_US
dc.contributor.authorEnstrom, Mark R.en_US
dc.contributor.authorKiem, Hans-Peteren_US
dc.contributor.authorAdair, Jennifer E.en_US
dc.contributor.authorGottardo, Raphaëlen_US
dc.contributor.authorLinsley, Peter S.en_US
dc.contributor.authorTurtle, Cameron J.en_US
dc.coverage.spatialEnglanden_US
dc.date2019-12-04
dc.date.accessioned2020-04-28T13:45:44Z
dc.date.available2020-04-28T13:45:44Z
dc.date.issued2020-01-10
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/31924795
dc.identifier.citationAlyssa Sheih, Valentin Voillet, Laïla-Aïcha Hanafi, Hannah A DeBerg, Masanao Yajima, Reed Hawkins, Vivian Gersuk, Stanley R Riddell, David G Maloney, Martin E Wohlfahrt, Dnyanada Pande, Mark R Enstrom, Hans-Peter Kiem, Jennifer E Adair, Raphaël Gottardo, Peter S Linsley, Cameron J Turtle. 2020. "Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy.." Nat Commun, Volume 11, Issue 1, pp. 219. https://doi.org/10.1038/s41467-019-13880-1
dc.identifier.issn2041-1723
dc.identifier.urihttps://hdl.handle.net/2144/40388
dc.description.abstractChimeric antigen receptor (CAR) T-cell therapy has produced remarkable anti-tumor responses in patients with B-cell malignancies. However, clonal kinetics and transcriptional programs that regulate the fate of CAR-T cells after infusion remain poorly understood. Here we perform TCRB sequencing, integration site analysis, and single-cell RNA sequencing (scRNA-seq) to profile CD8+ CAR-T cells from infusion products (IPs) and blood of patients undergoing CD19 CAR-T immunotherapy. TCRB sequencing shows that clonal diversity of CAR-T cells is highest in the IPs and declines following infusion. We observe clones that display distinct patterns of clonal kinetics, making variable contributions to the CAR-T cell pool after infusion. Although integration site does not appear to be a key driver of clonal kinetics, scRNA-seq demonstrates that clones that expand after infusion mainly originate from infused clusters with higher expression of cytotoxicity and proliferation genes. Thus, we uncover transcriptional programs associated with CAR-T cell behavior after infusion.en_US
dc.format.extentp. 219en_US
dc.languageeng
dc.language.isoen_US
dc.relation.ispartofNat Commun
dc.rights© The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAntigens, CD19en_US
dc.subjectClonal selection, antigen-mediateden_US
dc.subjectHumansen_US
dc.subjectImmunotherapyen_US
dc.subjectImmunotherapy, adoptiveen_US
dc.subjectKineticsen_US
dc.subjectNeoplasmsen_US
dc.subjectReceptors, antigen, T-cellen_US
dc.subjectReceptors, chimeric antigenen_US
dc.subjectSequence analysis, RNAen_US
dc.subjectT-lymphocytesen_US
dc.subjectT-Lymphocytes, cytotoxicen_US
dc.subjectTranscriptomeen_US
dc.titleClonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapyen_US
dc.typeArticleen_US
dc.description.versionPublished versionen_US
dc.identifier.doi10.1038/s41467-019-13880-1
pubs.elements-sourcepubmeden_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Arts & Sciencesen_US
pubs.organisational-groupBoston University, College of Arts & Sciences, Department of Mathematics & Statisticsen_US
pubs.publication-statusPublished onlineen_US
dc.identifier.mycv511295


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© The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.