Chimeric Antigen Receptor Structure and Manufacturing of Clinical Grade CAR Engineered Cells using Different Bioreactors
- PMID: 36395497
- DOI: 10.56875/2589-0646.1048
Chimeric Antigen Receptor Structure and Manufacturing of Clinical Grade CAR Engineered Cells using Different Bioreactors
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.
Similar articles
-
Platforms for Clinical-Grade CAR-T Cell Expansion.Methods Mol Biol. 2020;2086:139-150. doi: 10.1007/978-1-0716-0146-4_10. Methods Mol Biol. 2020. PMID: 31707673
-
CAR-T cell expansion platforms yield distinct T cell differentiation states.Cytotherapy. 2024 Jul;26(7):757-768. doi: 10.1016/j.jcyt.2024.03.003. Epub 2024 Mar 12. Cytotherapy. 2024. PMID: 38625071
-
Engineering strategies to overcome the current roadblocks in CAR T cell therapy.Nat Rev Clin Oncol. 2020 Mar;17(3):147-167. doi: 10.1038/s41571-019-0297-y. Epub 2019 Dec 17. Nat Rev Clin Oncol. 2020. PMID: 31848460 Free PMC article. Review.
-
Strategies for manufacturing cell therapy products aligned with patient needs.Methods Cell Biol. 2022;167:203-226. doi: 10.1016/bs.mcb.2021.11.003. Epub 2021 Dec 13. Methods Cell Biol. 2022. PMID: 35152997
-
Recent advances in the production, reprogramming, and application of CAR-T cells for treating hematological malignancies.Life Sci. 2022 Nov 15;309:121016. doi: 10.1016/j.lfs.2022.121016. Epub 2022 Sep 28. Life Sci. 2022. PMID: 36179813 Review.
Cited by
-
Promises and challenges of a decentralized CAR T-cell manufacturing model.Front Transplant. 2023 Sep 5;2:1238535. doi: 10.3389/frtra.2023.1238535. eCollection 2023. Front Transplant. 2023. PMID: 38993860 Free PMC article. Review.
-
Point-of-care manufacturing of anti-CD19 CAR-T cells using a closed production platform: Experiences of an academic in Thailand.Mol Ther Oncol. 2024 Oct 5;32(4):200889. doi: 10.1016/j.omton.2024.200889. eCollection 2024 Dec 19. Mol Ther Oncol. 2024. PMID: 39507317 Free PMC article.
-
Recent Findings on Therapeutic Cancer Vaccines: An Updated Review.Biomolecules. 2024 Apr 21;14(4):503. doi: 10.3390/biom14040503. Biomolecules. 2024. PMID: 38672519 Free PMC article. Review.
-
Advanced therapy medicinal products in China: Regulation and development.MedComm (2020). 2023 Apr 26;4(3):e251. doi: 10.1002/mco2.251. eCollection 2023 Jun. MedComm (2020). 2023. PMID: 37125239 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources