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Title: In-situ scalable manufacturing of Epstein-Barr virus-specific T-cells using bioreactor with an expandable culture area (BECA)
Authors: Chen, Sixun
Ahmad Amirul Bin Abdul Rahim
Wang, Who-Whong
Cheong, Rachael
Prabhu, Akshaya V.
Tan, Jerome Zu Yao
Naing, May Win
Toh, Han Chong
Liu, Dan
Keywords: Engineering::Bioengineering
Issue Date: 2022
Source: Chen, S., Ahmad Amirul Bin Abdul Rahim, Wang, W., Cheong, R., Prabhu, A. V., Tan, J. Z. Y., Naing, M. W., Toh, H. C. & Liu, D. (2022). In-situ scalable manufacturing of Epstein-Barr virus-specific T-cells using bioreactor with an expandable culture area (BECA). Scientific Reports, 12(1), 7045-.
Project: H18/01/a0/022 
Journal: Scientific Reports 
Abstract: The ex-vivo expansion of antigen-specific T-cells for adoptive T-cell immunotherapy requires active interaction between T-cells and antigen-presenting cells therefore culture density and environment become important variables to control. Maintenance of culture density in a static environment is traditionally performed by the expansion of the culture area through splitting of culture from a single vessel into multiple vessels-a highly laborious process. This study aims to validate the use and efficacy of a novel bioreactor, bioreactor with an expandable culture area-dual chamber (BECA-D), that was designed and developed with a cell chamber with expandable culture area (12-108 cm2) and a separate media chamber to allow for in-situ scaling of culture with maintenance of optimum culture density and improved nutrient and gas exchange while minimizing disturbance to the culture. The performance of BECA-D in the culture of Epstein-Barr virus-specific T-cells (EBVSTs) was compared to the 24-well plate. BECA-D had 0.9-9.7 times the average culture yield of the 24-well plates across 5 donor sets. BECA-D was able to maintain the culture environment with relatively stable glucose and lactate levels as the culture expanded. This study concludes that BECA-D can support the culture of ex-vivo EBVSTs with lower manufacturing labour and time requirements compared to the use of the 24-well plate. BECA-D and its adaptation into a closed system with an automated platform (currently being developed) provides cell therapy manufacturers and developers with a closed scale-out solution to producing adoptive cell therapy for clinical use.
ISSN: 2045-2322
DOI: 10.1038/s41598-022-11015-z
Schools: School of Chemical and Biomedical Engineering 
Organisations: Bioprocessing Technology Institute, A*STAR 
Rights: © The Author(s) 2022. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SCBE Journal Articles

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