Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy

Understanding factors that impact CAR T cell expansion in the clinic is crucial to improving its therapeutic success. Here the authors document heterogeneity in the clonal dynamics of CAR-T cells by tracking individual clones using the endogenous TCR and integration sites and provide further insight...

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Main Authors: Alyssa 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
Format: Article
Language:English
Published: Nature Publishing Group 2020-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-019-13880-1
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spelling doaj-9a5dfb14385d4c6ba59269c0303b61902021-05-11T09:11:16ZengNature Publishing GroupNature Communications2041-17232020-01-0111111310.1038/s41467-019-13880-1Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapyAlyssa Sheih0Valentin Voillet1Laïla-Aïcha Hanafi2Hannah A. DeBerg3Masanao Yajima4Reed Hawkins5Vivian Gersuk6Stanley R. Riddell7David G. Maloney8Martin E. Wohlfahrt9Dnyanada Pande10Mark R. Enstrom11Hans-Peter Kiem12Jennifer E. Adair13Raphaël Gottardo14Peter S. Linsley15Cameron J. Turtle16Clinical Research Division, Fred Hutchinson Cancer Research CenterVaccine and Infectious Disease Division and Public Health Sciences Division, Fred Hutchinson Cancer Research CenterClinical Research Division, Fred Hutchinson Cancer Research CenterBenaroya Research Institute at Virginia MasonDepartment of Mathematics and Statistics, Boston UniversityClinical Research Division, Fred Hutchinson Cancer Research CenterBenaroya Research Institute at Virginia MasonClinical Research Division, Fred Hutchinson Cancer Research CenterClinical Research Division, Fred Hutchinson Cancer Research CenterClinical Research Division, Fred Hutchinson Cancer Research CenterClinical Research Division, Fred Hutchinson Cancer Research CenterClinical Research Division, Fred Hutchinson Cancer Research CenterClinical Research Division, Fred Hutchinson Cancer Research CenterClinical Research Division, Fred Hutchinson Cancer Research CenterVaccine and Infectious Disease Division and Public Health Sciences Division, Fred Hutchinson Cancer Research CenterBenaroya Research Institute at Virginia MasonClinical Research Division, Fred Hutchinson Cancer Research CenterUnderstanding factors that impact CAR T cell expansion in the clinic is crucial to improving its therapeutic success. Here the authors document heterogeneity in the clonal dynamics of CAR-T cells by tracking individual clones using the endogenous TCR and integration sites and provide further insights into the role of transcriptional states in clonal kinetics.https://doi.org/10.1038/s41467-019-13880-1
collection DOAJ
language English
format Article
sources DOAJ
author Alyssa 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
spellingShingle Alyssa 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
Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy
Nature Communications
author_facet Alyssa 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
author_sort Alyssa Sheih
title Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy
title_short Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy
title_full Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy
title_fullStr Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy
title_full_unstemmed Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy
title_sort clonal kinetics and single-cell transcriptional profiling of car-t cells in patients undergoing cd19 car-t immunotherapy
publisher Nature Publishing Group
series Nature Communications
issn 2041-1723
publishDate 2020-01-01
description Understanding factors that impact CAR T cell expansion in the clinic is crucial to improving its therapeutic success. Here the authors document heterogeneity in the clonal dynamics of CAR-T cells by tracking individual clones using the endogenous TCR and integration sites and provide further insights into the role of transcriptional states in clonal kinetics.
url https://doi.org/10.1038/s41467-019-13880-1
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