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

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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/.
Date Issued
2020-01-10
Publisher Version
10.1038/s41467-019-13880-1
Author(s)
Sheih, Alyssa
Voillet, Valentin
Hanafi, Laïla-Aïcha
DeBerg, Hannah A.
Yajima, Masanao
Hawkins, Reed
Gersuk, Vivian
Riddell, Stanley R.
Maloney, David G.
Wohlfahrt, Martin E.
Pande, Dnyanada
Enstrom, Mark R.
Kiem, Hans-Peter
Adair, Jennifer E.
Gottardo, Raphaël
Linsley, Peter S.
Turtle, Cameron J.
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https://hdl.handle.net/2144/40388
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Published version
Citation (published version)
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. 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
Abstract
Chimeric 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.
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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/.
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