{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ueda T"],"funding":["National Cancer Center Research Fund","Japan Agency for Medical Research and Development","Japan Agency for Medical Research and Development (AMED)"],"pagination":["24-37"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9870784"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(1)"],"pubmed_abstract":["The effectiveness of chimaeric antigen receptor (CAR) T-cell immunotherapies against solid tumours relies on the accumulation, proliferation and persistency of T cells at the tumour site. Here we show that the proliferation of CD8αβ cytotoxic CAR T cells in solid tumours can be enhanced by deriving and expanding them from a single human induced-pluripotent-stem-cell clone bearing a CAR selected for efficient differentiation. We also show that the proliferation and persistency of the effector cells in the tumours can be further enhanced by genetically knocking out diacylglycerol kinase, which inhibits antigen-receptor signalling, and by transducing the cells with genes encoding for membrane-bound interleukin-15 (IL-15) and its receptor subunit IL-15Rα. In multiple tumour-bearing animal mode"],"journal":["Nature biomedical engineering"],"pubmed_title":["Optimization of the proliferation and persistency of CAR T cells derived from human induced pluripotent stem cells."],"pmcid":["PMC9870784"],"funding_grant_id":["Practical Research for Innovative Cancer Control","Core Center for iPS Cell Research","Development of Innovative 679 Research on Cancer Therapeutics"],"pubmed_authors":["Woltjen K","Minagawa A","Wang B","Shiina S","Kabai R","Ueda T","Watanabe A","Xu H","Tamada K","Kaneko S","Ohara K","Kodama Y","Nakatsura T","Kawai Y","Hotta A","Iriguchi S","Terakura S","Sakamoto S","Seno H","Uemura Y"],"additional_accession":[]},"is_claimable":false,"name":"Optimization of the proliferation and persistency of CAR T cells derived from human induced pluripotent stem cells.","description":"The effectiveness of chimaeric antigen receptor (CAR) T-cell immunotherapies against solid tumours relies on the accumulation, proliferation and persistency of T cells at the tumour site. Here we show that the proliferation of CD8αβ cytotoxic CAR T cells in solid tumours can be enhanced by deriving and expanding them from a single human induced-pluripotent-stem-cell clone bearing a CAR selected for efficient differentiation. We also show that the proliferation and persistency of the effector cells in the tumours can be further enhanced by genetically knocking out diacylglycerol kinase, which inhibits antigen-receptor signalling, and by transducing the cells with genes encoding for membrane-bound interleukin-15 (IL-15) and its receptor subunit IL-15Rα. In multiple tumour-bearing animal mode","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2025-04-04T13:08:37.84Z","creation":"2025-04-04T13:08:37.84Z"},"accession":"S-EPMC9870784","cross_references":{"pubmed":["36509913"],"doi":["10.1038/s41551-022-00969-0"]}}