A high-density microfluidic bioreactor for the automated manufacturing of CAR T cells.

Autor: Sin WX; Critical Analytics for Manufacturing Personalized-Medicine (CAMP), Singapore-MIT Alliance for Research and Technology Centre (SMART), Singapore, Singapore., Jagannathan NS; Critical Analytics for Manufacturing Personalized-Medicine (CAMP), Singapore-MIT Alliance for Research and Technology Centre (SMART), Singapore, Singapore.; Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore., Teo DBL; Critical Analytics for Manufacturing Personalized-Medicine (CAMP), Singapore-MIT Alliance for Research and Technology Centre (SMART), Singapore, Singapore., Kairi F; Critical Analytics for Manufacturing Personalized-Medicine (CAMP), Singapore-MIT Alliance for Research and Technology Centre (SMART), Singapore, Singapore., Fong SY; Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Tan JHL; Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Sandikin D; Critical Analytics for Manufacturing Personalized-Medicine (CAMP), Singapore-MIT Alliance for Research and Technology Centre (SMART), Singapore, Singapore., Cheung KW; Critical Analytics for Manufacturing Personalized-Medicine (CAMP), Singapore-MIT Alliance for Research and Technology Centre (SMART), Singapore, Singapore., Luah YH; Critical Analytics for Manufacturing Personalized-Medicine (CAMP), Singapore-MIT Alliance for Research and Technology Centre (SMART), Singapore, Singapore., Wu X; Critical Analytics for Manufacturing Personalized-Medicine (CAMP), Singapore-MIT Alliance for Research and Technology Centre (SMART), Singapore, Singapore., Raymond JJ; Critical Analytics for Manufacturing Personalized-Medicine (CAMP), Singapore-MIT Alliance for Research and Technology Centre (SMART), Singapore, Singapore., Lim FLWI; Advanced Cell Therapy and Research Institute, Singapore (ACTRIS), Consortium for Clinical Research and Innovation, Singapore (CRIS), Singapore, Singapore.; Department of Haematology, Singapore General Hospital, Singapore, Singapore.; SingHealth Duke-NUS Oncology Academic Clinical Programme, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore.; SingHealth Duke-NUS Cell Therapy Centre, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore., Lee YH; Critical Analytics for Manufacturing Personalized-Medicine (CAMP), Singapore-MIT Alliance for Research and Technology Centre (SMART), Singapore, Singapore.; SingHealth Duke-NUS Cell Therapy Centre, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore., Seng MS; SingHealth Duke-NUS Oncology Academic Clinical Programme, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore.; SingHealth Duke-NUS Cell Therapy Centre, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore.; Department of Paediatric Haematology and Oncology, KK Women's and Children's Hospital, Singapore, Singapore., Soh SY; SingHealth Duke-NUS Oncology Academic Clinical Programme, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore.; SingHealth Duke-NUS Cell Therapy Centre, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore.; Department of Paediatric Haematology and Oncology, KK Women's and Children's Hospital, Singapore, Singapore., Chen Q; Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Ram RJ; Critical Analytics for Manufacturing Personalized-Medicine (CAMP), Singapore-MIT Alliance for Research and Technology Centre (SMART), Singapore, Singapore. rajeev@mit.edu.; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA. rajeev@mit.edu., Tucker-Kellogg L; Critical Analytics for Manufacturing Personalized-Medicine (CAMP), Singapore-MIT Alliance for Research and Technology Centre (SMART), Singapore, Singapore. tuckerNUS@gmail.com.; Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore, Singapore. tuckerNUS@gmail.com., Birnbaum ME; Critical Analytics for Manufacturing Personalized-Medicine (CAMP), Singapore-MIT Alliance for Research and Technology Centre (SMART), Singapore, Singapore. mbirnb@mit.edu.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. mbirnb@mit.edu.; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA. mbirnb@mit.edu.; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. mbirnb@mit.edu.
Jazyk: angličtina
Zdroj: Nature biomedical engineering [Nat Biomed Eng] 2024 Jun 04. Date of Electronic Publication: 2024 Jun 04.
DOI: 10.1038/s41551-024-01219-1
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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