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Cited by 18CAR-T cell therapy researchImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

Chimeric antigen receptor structure and manufacturing of clinical grade CAR engineered cells using different bioreactors

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Syed, Farhatullah, El Fakih, Riad, Alahmari, Ali D., Ali, Ahmed S. Osman, Aljurf, Mahmoud·2022·Hematology/Oncology and Stem Cell Therapy
DOI 10.56875/2589-0646.1048
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Abstract

Increasing success of adaptive cell therapy (ACT), such as genetically engineered T cells to express chimeric antigen receptors (CARs) proven to be highly significant technological advancements and impressive clinical outcomes in selected haematological malignancies, with promising efficacy. The evolution of CAR designs beyond the conventional structures is necessary to address some of the limitations of conventional CAR therapy and to expand the use of CAR T cells to a wider range of malignancies. There are various obstacles with a wide range of engineering strategies in order to improve the safety, efficacy and applicability of this therapeutic modality. Here we describe details of modular CAR structure with all the necessary domains and what is known about proximal CAR signalling in T cells. Furthermore, the global need for adoptive cell therapy is expanding very rapidly, and there is an urgent increasing demand for fully automated manufacturing methods that can produce large scale clinical grade high quality CAR engineered immune cells. Despite the advances in automation for the production of clinical grade CAR engineered cells, the manufacturing process is costly, consistent and involves multiple steps, including selection, activation, transduction, and Ex-Vivo expansion. Among these complex manufacturing phases, the choice of culture system to generate a high number of functional cells needs to be evaluated and optimized. Here we list the most advance fully automated to semi-automated bioreactor platforms can be used for the production of clinical grade CAR engineered cells for clinical trials but are far from being standardized. New processing options are available and a systematic effort seeking automation, standardization and the increase of production scale, would certainly help to bring the costs down and ultimately democratise this personalized therapy. In this review, we describe in detail different CAR engineered T cell platforms available and can be used in future for clinical-grade CAR engineered ATMP production.

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References 21 · Cited by 18

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Authors
Syed, F., El Fakih, R., Alahmari, A. D., Ali, A. S. O., & Aljurf, M.
Affiliations
King Faisal Specialist Hospital & Research Centre (SA)
Corresponding author
Syed, Farhatullah
ORCID
Venue
Hematology/Oncology and Stem Cell Therapy
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2022-07
Volume
15
Issue
3
Pages
137-152
ISSN
1658-3876 (ISSN-L)
DOI
10.56875/2589-0646.1048
OpenAlex
W4309517263
Cited by
18
References
21
Citations by year
2026: 4 · 2025: 8 · 2024: 3 · 2023: 3
FWCI
1.47
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • Hematology/Oncology and Stem Cell Therapy (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
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, chimeric antigen receptor T cells, CAR structure, bioreactors, ex vivo T cell expansion, adoptive immunotherapy, automated manufacturing, clinical-grade cell products, hematologic malignancies
MeSH terms
Receptors, Chimeric Antigen, Humans, T-Lymphocytes, Immunotherapy, Adoptive, Bioreactors, Cell- and Tissue-Based Therapy

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