# Engineering the next-generation of CAR T-cells with CRISPR-Cas9 gene editing

> This review evaluates several of the ongoing and future directions of combining next-generation CRISPR-Cas9 gene editing with synthetic biology to optimize CAR T-cell therapy for future clinical trials toward the establishment of a new cancer treatment paradigm.

## Metadata
- Authors: Alexander J Dimitri, F. Herbst, J. Fraietta
- Journal: Molecular Cancer
- Published: 2022
- DOI: https://doi.org/10.1186/s12943-022-01559-z
- Citations: 269
- Source: Semantic Scholar
- Access: Open Access

## Technology Hub
- Hub: CRISPR Gene Editing
- Discipline: Biology / Genetics
- Hub URL: https://science-database.com/technology/crispr
- Hub llms.txt: https://science-database.com/technology/crispr/llms.txt

## Abstract
Chimeric Antigen Receptor (CAR) T-cells represent a breakthrough in personalized cancer therapy. In this strategy, synthetic receptors comprised of antigen recognition, signaling, and costimulatory domains are used to reprogram T-cells to target tumor cells for destruction. Despite the success of this approach in refractory B-cell malignancies, optimal potency of CAR T-cell therapy for many other cancers, particularly solid tumors, has not been achieved. Factors such as T-cell exhaustion, lack of CAR T-cell persistence, cytokine-related toxicities, and bottlenecks in the manufacturing of autologous products have hampered the safety, effectiveness, and availability of this approach. With the ease and accessibility of CRISPR-Cas9-based gene editing, it is possible to address many of these limitations. Accordingly, current research efforts focus on precision engineering of CAR T-cells with conventional CRISPR-Cas9 systems or novel editors that can install desired genetic changes with or without introduction of a double-stranded break (DSB) into the genome. These tools and strategies can be directly applied to targeting negative regulators of T-cell function, directing therapeutic transgenes to specific genomic loci, and generating reproducibly safe and potent allogeneic universal CAR T-cell products for on-demand cancer immunotherapy. This review evaluates several of the ongoing and future directions of combining next-generation CRISPR-Cas9 gene editing with synthetic biology to optimize CAR T-cell therapy for future clinical trials toward the establishment of a new cancer treatment paradigm.

## Links
- DOI: https://doi.org/10.1186/s12943-022-01559-z
- Semantic Scholar: https://www.semanticscholar.org/paper/5d923eebf9f2306e65ee75710a4468189c784dfc
- PDF: https://molecular-cancer.biomedcentral.com/track/pdf/10.1186/s12943-022-01559-z
- JSON API: https://science-database.com/api/v1/technology/crispr

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Paper ID: s2-5d923eebf9f2306e65ee75710a4468189c784dfc | Hub: crispr