Potential solutions for manufacture of CAR T cells in cancer immunotherapy

Blache, Ulrich; Popp, Georg; Dünkel, Anna; Koehl, Ulrike; Stephan, Frank

doi:10.1038/s41467-022-32866-0

Cited by 81 publications

(53 citation statements)

References 20 publications

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“…To overcome safety concerns and time-and cost-intensive manufacturing processes under higher biosafety levels, the mRNA-based, transient CAR-T cell generation is an attractive alternative approach to the currently approved CAR-T products, which are generated by viral transduction [23][24][25][26] .…”

Section: Discussionmentioning

confidence: 99%

How to improve mRNA-based CAR-T cell generation and functionality? A lab-scale comparison

Auw

Serfling

Kitte

et al. 2023

Preprint

Self Cite

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Process development for transferring lab-scale research workflows to automated manufacturing procedures is critical chimeric antigen receptor (CAR)-T cell therapies. Thereby, the key factor for cell viability, expansion, modification, and functionality is the optimal combination of medium and T cell activator as well as their regulatory compliance for later manufacturing under Good Manufacturing Practice (GMP). In this study, we compared two protocols for CAR-mRNA-modified T cell generation using our current lab-scale process, analyzed all mentioned parameters, and evaluated the protocols’ potential for upscaling and process development of mRNA-based CAR-T cell therapies.

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Section: Discussionmentioning

confidence: 99%

How to improve mRNA-based CAR-T cell generation and functionality? A lab-scale comparison

Auw

Serfling

Kitte

et al. 2023

Preprint

Self Cite

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show abstract

“…Several distinct approaches attempt to resolve various problematic aspects of CAR T treatments. Some include strategies to shorten the lengthy manufacturing period for autologous infusion [ 90 ]; others use low-affinity CARs that reduce on-target off-tumor toxicity [ 91 ]; others target tumor-supporting cells like Tregs, TAMs, and MDSCs [ 92 ]; and others potentiate therapy by adding stimulators like bispecific T cell engagers (BiTEs), marked antibodies [ 25 ], etc. This chapter, however, will focus on yet another promising set of concepts of impressive ingenuity.…”

Section: Innovative Researchmentioning

confidence: 99%

CAR T Cell Therapy: A Versatile Living Drug

Marco

Monzó

Ojala

2023

IJMS

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After seeing a dramatic increase in the development and use of immunotherapy and precision medicine over the past few decades, oncological care now embraces the start of the adoptive cell therapy (ACT) era. This impulse towards a new treatment paradigm has been led by chimeric antigen receptor (CAR) T cells, the only type of ACT medicinal product to be commercialized so far. Brought about by an ever-growing understanding of cellular engineering, CAR T cells are T lymphocytes genetically modified with an appropriate DNA construct, which endows them with expression of a CAR, a fusion protein between a ligand-specific recognition domain, often an antibody-like structure, and the activating signaling domain of the T cell receptor. Through this genetic enhancement, CAR T cells are engineered from a cancer patient’s own lymphocytes to better target and kill their cancer cells, and the current amassed data on clinical outcomes point to a stream of bright developments in the near future. Herein, from concept design and present-day manufacturing techniques to pressing hurdles and bright discoveries around the corner, we review and thoroughly describe the state of the art in CAR T cell therapy.

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“…Manufacturing of modified T cells is a multi-step process (13). The focus of two main areas of optimizing T-cell therapies are designing optimal genetic modifications of T cells and engineering improved cell activation and culture processes during ex vivo T-cell expansion (14).…”

Section: Introductionmentioning

confidence: 99%

The magic of small-molecule drugs during ex vivo expansion in adoptive cell therapy

et al. 2023

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In the past decades, advances in the use of adoptive cellular therapy to treat cancer have led to unprecedented responses in patients with relapsed/refractory or late-stage malignancies. However, cellular exhaustion and senescence limit the efficacy of FDA-approved T-cell therapies in patients with hematologic malignancies and the widespread application of this approach in treating patients with solid tumors. Investigators are addressing the current obstacles by focusing on the manufacturing process of effector T cells, including engineering approaches and ex vivo expansion strategies to regulate T-cell differentiation. Here we reviewed the current small-molecule strategies to enhance T-cell expansion, persistence, and functionality during ex vivo manufacturing. We further discussed the synergistic benefits of the dual-targeting approaches and proposed novel vasoactive intestinal peptide receptor antagonists (VIPR-ANT) peptides as emerging candidates to enhance cell-based immunotherapy.

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Potential solutions for manufacture of CAR T cells in cancer immunotherapy

Abstract: CAR T cell therapy is an effective cancer treatment, but biological and manufacturing hurdles hamper its broad breakthrough. Although the first step towards automated manufacture of CAR cells has been taken, new technologies are needed to enable the treatment of large patient groups.

Cited by 81 publications

References 20 publications

How to improve mRNA-based CAR-T cell generation and functionality? A lab-scale comparison

How to improve mRNA-based CAR-T cell generation and functionality? A lab-scale comparison

CAR T Cell Therapy: A Versatile Living Drug

The magic of small-molecule drugs during ex vivo expansion in adoptive cell therapy

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