Manufacturing chimeric antigen receptor T cells: issues and challenges
Open accessAbstract
Clinical trials of adoptively transferred CD19 chimeric antigen receptor (CAR) T cells have delivered unprecedented responses in patients with relapsed refractory B-cell malignancy. These results have prompted Food and Drug Administration (FDA) approval of two CAR T-cell products in this high-risk patient population. The widening range of indications for CAR T-cell therapy and increasing patient numbers present a significant logistical challenge to manufacturers aiming for reproducible delivery systems for high-quality clinical CAR T-cell products. This review discusses current and novel CAR T-cell processing methodologies and the quality control systems needed to meet the increasing clinical demand for these exciting new therapies.
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Conventional CAR-T manufacturing involves many hands-on, manual operations and open steps in grade A laminar flow cabinets in a dedicated grade B cleanroom.
“Conventional CAR-T manufacturing involves many hands-on, manual operations and open steps in grade A laminar flow cabinets in a dedicated grade B cleanroom.6,7”
From Point-of-care manufacturing of anti-CD19 CAR-T cells using a closed production platform: Experiences of an academic in Thailand (2024) · cites this paper as [7]
The “Closed systems and automated platforms” section describes automated, closed systems used for CAR-T production, but does not describe conventional CAR-T manufacturing as manual or open. Searches for grade B cleanrooms and laminar-flow cabinets found no passage supporting those details; page numbers were unavailable in our copy. (LLM, conf=0.72)
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“6,7 A paradigm shift enabling POC manufacturing is the development of bioreactors and closed system manufacturing platforms that mitigate the need for expensive infrastructure and simplify the multistep process.”
Sotomayor, P., Prochazka, L., & Brockhaus, M. (2022) · Pharma Research · doi:10.62655/s-epub.2022.v14.i01.pp53-62
- Authors
- Roddie, C., O'Reilly, M., Dias Alves Pinto, J., Vispute, K., & Lowdell, M.
- Affiliations
- National Health Service (GB)
- University College London (GB)
- Corresponding author
- Roddie, Claire
- Venue
- Cytotherapy
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 21
- Issue
- 3
- Pages
- 327-340
- ISSN
- 1465-3249 (ISSN-L)
- OpenAlex
- W2914774688
- Cited by
- 168
- References
- 6
- Citations by year
- 2026: 19 · 2025: 24 · 2024: 30 · 2023: 18 · 2022: 22 · 2021: 27 · 2020: 21 · 2019: 7
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- green
- discovery.ucl.ac.uk
- Locations
- Cytotherapy (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Seventh Framework Programme (602239 ATECT)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- chimeric antigen receptor T cells, CAR T cell manufacturing, CD19, adoptive immunotherapy, B-cell malignancies, quality control, industrial scalability, reproducibility
- MeSH terms
- Manufacturing and Industrial Facilities, Receptors, Chimeric Antigen, Blood Component Removal, Cell Survival, Endotoxins, Humans, Lymphocyte Activation, Mycoplasma, Neoplasms, Quality Control, T-Lymphocytes, Transduction, Genetic, Cryopreservation, Immunotherapy, Adoptive, Antigens, CD19
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