{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["644(8075)"],"submitter":["Chen AXY"],"pubmed_abstract":["The efficacy of chimeric antigen receptor (CAR) T cell therapy in solid tumours is limited by immunosuppression and antigen heterogeneity<sup>1-3</sup>. To overcome these barriers, 'armoured' CAR T cells, which secrete proinflammatory cytokines, have been developed<sup>4</sup>. However, their clinical application has been limited because of toxicity related to peripheral expression of the armouring transgene<sup>5</sup>. Here, we have developed a CRISPR knock-in strategy that leverages the regulatory mechanisms of endogenous genes to drive transgene expression in a tumour-localized manner. By screening endogenous genes with tumour-restricted expression, we have identified the NR4A2 and RGS16 promoters as promising candidates to support the delivery of cytokines such as IL-12 and IL-2 direc"],"journal":["Nature"],"pagination":["241-251"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12328239"],"repository":["biostudies-literature"],"pubmed_title":["Rewiring endogenous genes in CAR T cells for tumour-restricted payload delivery."],"pmcid":["PMC12328239"],"pubmed_authors":["Lai J","Waithman J","Harrison SJ","Wiebking V","Porteus MH","Yap KM","Munoz I","Huang YK","Armitage JD","Middelburg J","Lee JN","Parish IA","Tong J","Hoang TX","van Elsas MJ","Mackay LK","Beavis PA","Chan CW","Scott AM","Todd KL","Li J","Sek K","Audsley KM","Oliaro J","House IG","Kim JS","Darcy PK","Dunbar PA","Derrick EB","Scheffler C","Nguyen D","Cole TJ","de Menezes MN","Chen AXY"],"additional_accession":[]},"is_claimable":false,"name":"Rewiring endogenous genes in CAR T cells for tumour-restricted payload delivery.","description":"The efficacy of chimeric antigen receptor (CAR) T cell therapy in solid tumours is limited by immunosuppression and antigen heterogeneity<sup>1-3</sup>. To overcome these barriers, 'armoured' CAR T cells, which secrete proinflammatory cytokines, have been developed<sup>4</sup>. However, their clinical application has been limited because of toxicity related to peripheral expression of the armouring transgene<sup>5</sup>. Here, we have developed a CRISPR knock-in strategy that leverages the regulatory mechanisms of endogenous genes to drive transgene expression in a tumour-localized manner. By screening endogenous genes with tumour-restricted expression, we have identified the NR4A2 and RGS16 promoters as promising candidates to support the delivery of cytokines such as IL-12 and IL-2 direc","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-04-13T08:17:01.979Z","creation":"2026-04-07T13:29:27.673Z"},"accession":"S-EPMC12328239","cross_references":{"pubmed":["40604285"],"doi":["10.1038/s41586-025-09212-7"]}}