{"id":"doi:10.1186/s12943-022-01559-z","kind":"review","title":"Engineering the next-generation of CAR T-cells with CRISPR-Cas9 gene editing","authors":["Alexander J. Dimitri","Friederike Herbst","Joseph A. Fraietta"],"author_count":3,"year":2022,"published":"2022-03-18","venue":"Molecular Cancer","cited_by":355,"doi":"10.1186/s12943-022-01559-z","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1186/s12943-022-01559-z","archive_url":"https://space-kitty.com/papers/doi:10.1186/s12943-022-01559-z","updated":null,"pmid":"35303871","pmcid":null,"openalex_id":"W4220766750","pdf_url":"https://molecular-cancer.biomedcentral.com/track/pdf/10.1186/s12943-022-01559-z","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.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["CAR-T cell therapy research"],"details":null,"provenance":"openalex","attribution":"Abstract of \"Engineering the next-generation of CAR T-cells with CRISPR-Cas9 gene editing\" by Alexander J. Dimitri, Friederike Herbst, Joseph A. Fraietta, https://doi.org/10.1186/s12943-022-01559-z, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"gene-editing-therapies","name":"CRISPR & Gene-Editing Therapies","domain_slug":"medicine"}],"cited_in_dossiers":[]}