{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Labanieh L"],"funding":["NCI NIH HHS"],"pagination":["1745-1763.e22"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9467936"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["185(10)"],"pubmed_abstract":["Regulatable CAR platforms could circumvent toxicities associated with CAR-T therapy, but existing systems have shortcomings including leakiness and attenuated activity. Here, we present SNIP CARs, a protease-based platform for regulating CAR activity using an FDA-approved small molecule. Design iterations yielded CAR-T cells that manifest full functional capacity with drug and no leaky activity in the absence of drug. In numerous models, SNIP CAR-T cells were more potent than constitutive CAR-T cells and showed diminished T cell exhaustion and greater stemness. In a ROR1-based CAR lethality model, drug cessation following toxicity onset reversed toxicity, thereby credentialing the platform as a safety switch. In the same model, reduced drug dosing opened a therapeutic window that resulted "],"journal":["Cell"],"pubmed_title":["Enhanced safety and efficacy of protease-regulated CAR-T cell receptors."],"pmcid":["PMC9467936"],"funding_grant_id":["DP2 CA272092","U54 CA232568","U01 CA260852"],"pubmed_authors":["Murty T","Mehta N","Pacheco KZB","Xu P","Parker KR","Chang HY","Vilches-Moure JG","Labanieh L","Cochran JR","Weber EW","Majzner RG","Yamada-Hunter SA","Sotillo E","Theruvath J","Heitzeneder S","Lin MZ","Malipatlolla M","Mackall CL","Satpathy AT","Fisher CJ","Klysz D","Hui JH"],"additional_accession":[]},"is_claimable":false,"name":"Enhanced safety and efficacy of protease-regulated CAR-T cell receptors.","description":"Regulatable CAR platforms could circumvent toxicities associated with CAR-T therapy, but existing systems have shortcomings including leakiness and attenuated activity. Here, we present SNIP CARs, a protease-based platform for regulating CAR activity using an FDA-approved small molecule. Design iterations yielded CAR-T cells that manifest full functional capacity with drug and no leaky activity in the absence of drug. In numerous models, SNIP CAR-T cells were more potent than constitutive CAR-T cells and showed diminished T cell exhaustion and greater stemness. In a ROR1-based CAR lethality model, drug cessation following toxicity onset reversed toxicity, thereby credentialing the platform as a safety switch. In the same model, reduced drug dosing opened a therapeutic window that resulted ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2026-05-28T03:41:04.288Z","creation":"2025-04-05T21:07:43.538Z"},"accession":"S-EPMC9467936","cross_references":{"pubmed":["35483375"],"doi":["10.1016/j.cell.2022.03.041"]}}