| RRC ID |
78712
|
| 著者 |
Lu X, Lofgren SM, Zhao Y, Mazur PK.
|
| タイトル |
Multiplexed transcriptomic profiling of the fate of human CAR T cells in vivo via genetic barcoding with shielded small nucleotides.
|
| ジャーナル |
Nat Biomed Eng
|
| Abstract |
The design of chimeric antigen receptor (CAR) T cells would benefit from knowledge of the fate of the cells in vivo. This requires the permanent labelling of CAR T cell products and their pooling in the same microenvironment. Here, we report a cell-barcoding method for the multiplexed longitudinal profiling of cells in vivo using single-cell RNA sequencing (scRNA-seq). The method, which we named shielded-small-nucleotide-based scRNA-seq (SSN-seq), is compatible with both 3' and 5' single-cell profiling, and enables the recording of cell identity, from cell infusion to isolation, by leveraging the ubiquitous Pol III U6 promoters to robustly express small-RNA barcodes modified with direct-capture sequences. By using SSN-seq to track the dynamics of the states of CAR T cells in a tumour-rechallenge mouse model of leukaemia, we found that a combination of cytokines and small-molecule inhibitors that are used in the ex vivo manufacturing of CAR T cells promotes the in vivo expansion of persistent populations of CD4+ memory T cells. By facilitating the probing of cell-state dynamics in vivo, SSN-seq may aid the development of adoptive cell therapies.
|
| 巻・号 |
7(9)
|
| ページ |
1170-1187
|
| 公開日 |
2023-9-1
|
| DOI |
10.1038/s41551-023-01085-3
|
| PII |
10.1038/s41551-023-01085-3
|
| PMID |
37652986
|
| MeSH |
Animals
CD4-Positive T-Lymphocytes*
Cell- and Tissue-Based Therapy
Cytokines
Humans
Mice
Nucleotides
Transcriptome*
|
| リソース情報 |
| ヒト・動物細胞 |
K562(RCB0027)
NALM-6(RCB1933) |
