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| Status |
Public on May 29, 2024 |
| Title |
A high-density microfluidic bioreactor for the automated manufacturing of CAR T cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The manufacturing of autologous chimaeric antigen receptor (CAR) T cells largely relies either on fed-batch and manual processes that often lack environmental monitoring and control or on bioreactors that cannot be easily scaled out to meet patient demands. Here we show that human primary T cells can be activated, transduced and expanded to high densities in a 2 ml automated closed-system microfluidic bioreactor to produce viable anti-CD19 CAR T cells (specifically, more than 60 million CAR T cells from donor cells derived from patients with lymphoma and more than 200 million CAR T cells from healthy donors). The in vitro secretion of cytokines, the short-term cytotoxic activity and the long-term persistence and proliferation of the cell products, as well as their in vivo anti-leukaemic activity, were comparable to those of T cells produced in a gas-permeable well. The manufacturing-process intensification enabled by the miniaturized perfusable bioreactor may facilitate the analysis of the growth and metabolic states of CAR T cells during ex vivo culture, the high-throughput optimization of cell-manufacturing processes and the scale-out of cell-therapy manufacturing.
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| Overall design |
Comparative gene expression profiling analysis of bulk RNA-seq data for microbioreactor (MBR) cell products versus gas-permeable well plate (GWP) cell products, each from three biological replicates (donors A, B, C).
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| Web link |
https://www.nature.com/articles/s41551-024-01219-1
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| Contributor(s) |
Sin WX, Jagannathan NS, Teo D, Kairi F, Fong SY, Tan J, Sandikin D, Cheung KW, Luah YH, Wu X, Raymond JJ, Lim F, Lee YH, Seng M, Soh SY, Chen Q, Ram RJ, Tucker-Kellogg L, Birnbaum ME |
| Citation(s) |
38834752 |
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| Submission date |
Mar 07, 2024 |
| Last update date |
Jun 05, 2024 |
| Contact name |
Wei-Xiang Sin |
| E-mail(s) |
weixiang.sin@smart.mit.edu
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| Organization name |
SMART
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| Street address |
1 CREATE Way, #04-13/14, Enterprise Wing
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| City |
Singapore |
| ZIP/Postal code |
138602 |
| Country |
Singapore |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1085289 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE261103_gene_count.xls.gz |
2.3 Mb |
(ftp)(http) |
XLS |
| GSE261103_gene_fpkm.xls.gz |
3.4 Mb |
(ftp)(http) |
XLS |
SRA Run Selector |
| Raw data are available in SRA |
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