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
Institution
Title
Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy.
Journal
Nature communications
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
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