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

Details

Serval ID
serval:BIB_530D7646DE87
Type
Article: article from journal or magazin.
Collection
Publications
Title
Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy.
Journal
Nature communications
Author(s)
Sheih A., Voillet V., Hanafi L.A., DeBerg H.A., Yajima M., Hawkins R., Gersuk V., Riddell S.R., Maloney D.G., Wohlfahrt M.E., Pande D., Enstrom M.R., Kiem H.P., Adair J.E., Gottardo R., Linsley P.S., Turtle C.J.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
10/01/2020
Peer-reviewed
Oui
Volume
11
Number
1
Pages
219
Language
english
Notes
Publication types: Clinical Trial, Phase I ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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 <sup>+</sup> 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.
Keywords
Antigens, CD19/immunology, Clonal Selection, Antigen-Mediated/immunology, Humans, Immunotherapy, Immunotherapy, Adoptive, Kinetics, Neoplasms/immunology, Neoplasms/therapy, Receptors, Antigen, T-Cell/immunology, Receptors, Chimeric Antigen/immunology, Sequence Analysis, RNA, T-Lymphocytes/immunology, T-Lymphocytes, Cytotoxic/immunology, Transcriptome
Pubmed
Web of science
Open Access
Yes
Create date
28/02/2022 12:45
Last modification date
23/03/2024 8:24
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