T cells modified for expression of Chimeric Antigen Receptors (CARs) were the first genemodified
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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:87691 |
| Date | 26 October 2023 |
| Creators | Wagner, Dimitrios L., Koehl, Ulrike, Chmielewski, Markus, Scheid, Christoph, Stripecke, Renata |
| Publisher | Frontiers Media S.A. |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 865424 |
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