Optimizing Manufacturing Protocols of Chimeric Antigen Receptor T Cells for Improved Anticancer Immunotherapy
1
Department of Internal Medicine V, Heidelberg University Hospital, 69120 Heidelberg, Germany
2
National Center for Tumor Diseases (NCT), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany
3
Oncology Business Unit—Medical Affairs, Takeda Pharma Vertrieb GmbH & Co. KG, 10117 Berlin, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(24), 6223; https://doi.org/10.3390/ijms20246223
Received: 8 November 2019 / Revised: 7 December 2019 / Accepted: 8 December 2019 / Published: 10 December 2019
(This article belongs to the Special Issue CAR-T Cell Therapy)
Chimeric antigen receptor (CAR) T cell therapy can achieve outstanding response rates in heavily pretreated patients with hematological malignancies. However, relapses occur and they limit the efficacy of this promising treatment approach. The cellular composition and immunophenotype of the administered CART cells play a crucial role for therapeutic success. Less differentiated CART cells are associated with improved expansion, long-term in vivo persistence, and prolonged anti-tumor control. Furthermore, the ratio between CD4+ and CD8+ T cells has an effect on the anti-tumor activity of CART cells. The composition of the final cell product is not only influenced by the CART cell construct, but also by the culturing conditions during ex vivo T cell expansion. This includes different T cell activation strategies, cytokine supplementation, and specific pathway inhibition for the differentiation blockade. The optimal production process is not yet defined. In this review, we will discuss the use of different CART cell production strategies and the molecular background for the generation of improved CART cells in detail.
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Keywords:
chimeric antigen receptor; CAR; CART; adoptive cell therapy; immunotherapy; T lymphocyte; CART cell production; T cell activation; cytokines
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MDPI and ACS Style
Stock, S.; Schmitt, M.; Sellner, L. Optimizing Manufacturing Protocols of Chimeric Antigen Receptor T Cells for Improved Anticancer Immunotherapy. Int. J. Mol. Sci. 2019, 20, 6223. https://doi.org/10.3390/ijms20246223
AMA Style
Stock S, Schmitt M, Sellner L. Optimizing Manufacturing Protocols of Chimeric Antigen Receptor T Cells for Improved Anticancer Immunotherapy. International Journal of Molecular Sciences. 2019; 20(24):6223. https://doi.org/10.3390/ijms20246223
Chicago/Turabian StyleStock, Sophia; Schmitt, Michael; Sellner, Leopold. 2019. "Optimizing Manufacturing Protocols of Chimeric Antigen Receptor T Cells for Improved Anticancer Immunotherapy" Int. J. Mol. Sci. 20, no. 24: 6223. https://doi.org/10.3390/ijms20246223
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