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

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 and Cameron J. Turtle ()
Additional contact information
Alyssa Sheih: Fred Hutchinson Cancer Research Center
Valentin Voillet: Fred Hutchinson Cancer Research Center
Laïla-Aïcha Hanafi: Fred Hutchinson Cancer Research Center
Hannah A. DeBerg: Benaroya Research Institute at Virginia Mason
Masanao Yajima: Boston University
Reed Hawkins: Fred Hutchinson Cancer Research Center
Vivian Gersuk: Benaroya Research Institute at Virginia Mason
Stanley R. Riddell: Fred Hutchinson Cancer Research Center
David G. Maloney: Fred Hutchinson Cancer Research Center
Martin E. Wohlfahrt: Fred Hutchinson Cancer Research Center
Dnyanada Pande: Fred Hutchinson Cancer Research Center
Mark R. Enstrom: Fred Hutchinson Cancer Research Center
Hans-Peter Kiem: Fred Hutchinson Cancer Research Center
Jennifer E. Adair: Fred Hutchinson Cancer Research Center
Raphaël Gottardo: Fred Hutchinson Cancer Research Center
Peter S. Linsley: Benaroya Research Institute at Virginia Mason
Cameron J. Turtle: Fred Hutchinson Cancer Research Center

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-13880-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13880-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-13880-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().