Universität zu Köln

Wagner, Dimitrios L., Koehl, Ulrike, Chmielewski, Markus, Scheid, Christoph and Stripecke, Renata (2022). Review: Sustainable Clinical Development of CAR-T Cells - Switching From Viral Transduction Towards CRISPR-Cas Gene Editing. Front. Immunol., 13. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-3224

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Abstract

T cells modified for expression of Chimeric Antigen Receptors (CARs) were the first gene-modified cell products approved for use in cancer immunotherapy. CAR-T cells engineered with gammaretroviral or lentiviral vectors (RVs/LVs) targeting B-cell lymphomas and leukemias have shown excellent clinical efficacy and no malignant transformation due to insertional mutagenesis to date. Large-scale production of RVs/LVs under good-manufacturing practices for CAR-T cell manufacturing has soared in recent years. However, manufacturing of RVs/LVs remains complex and costly, representing a logistical bottleneck for CAR-T cell production. Emerging gene-editing technologies are fostering a new paradigm in synthetic biology for the engineering and production of CAR-T cells. Firstly, the generation of the modular reagents utilized for gene editing with the CRISPR-Cas systems can be scaled-up with high precision under good manufacturing practices, are interchangeable and can be more sustainable in the long-run through the lower material costs. Secondly, gene editing exploits the precise insertion of CARs into defined genomic loci and allows combinatorial gene knock-ins and knock-outs with exciting and dynamic perspectives for T cell engineering to improve their therapeutic efficacy. Thirdly, allogeneic edited CAR-effector cells could eventually become available as off-the-shelf products. This review addresses important points to consider regarding the status quo, pending needs and perspectives for the forthright evolution from the viral towards gene editing developments for CAR-T cells.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wagner, Dimitrios L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koehl, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Chmielewski, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Scheid, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Stripecke, Renata UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-690628
DOI:	10.3389/fimmu.2022.865424
Journal or Publication Title:	Front. Immunol.
Volume:	13
Date:	2022
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-3224
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RETROVIRAL VECTORS; LENTIVIRAL VECTORS; THERAPY; GENERATION; MULTICENTER; CHALLENGES; RECEPTORS; LYMPHOMAS; DESIGN; TRUCKS Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69062