A high-density microfluidic bioreactor for the automated manufacturing of CAR T cells.
Nat Biomed Eng
; 2024 Jun 04.
Article
in En
| MEDLINE
| ID: mdl-38834752
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Nat Biomed Eng
Year:
2024
Document type:
Article
Affiliation country:
Singapore