{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Balke-Want H"],"funding":["Parker Institute for Cancer Immunotherapy","Saint Baldricks Foundation","German Research Foundation","Ministerium für Kultur und Wissenschaft des Landes Nordrhein-Westfalen","Mark Foundation For Cancer Research","Else Kroner-Fresenius Foundation","University of Cologne Center for Molecular Medicine Cologne","NCI NIH HHS","National Institutes of Health","Virginia and D K Ludwig Fund for Cancer Research"],"pagination":["102549"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12866126"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(1)"],"pubmed_abstract":["Small cell lung cancer (SCLC), a highly lethal disease, limits T cell responses by downregulating major histocompatibility (MHC) class I molecules. Because chimeric antigen receptor (CAR) T cells are not MHC restricted, they may provide a powerful strategy against SCLC. However, few CAR targets for SCLC are known. Here, we show that B7-H3/CD276 is expressed in SCLC and thoracic SMARCA4-deficient undifferentiated tumors (UTs) that can clinicopathologically mimic SCLC. Thoracic SMARCA4-deficient UTs limit killing by B7-H3 CAR T cells via secretion of transforming growth factor β1 (TGF-β1). To overcome tumor-driven CAR T cell suppression, we knock in c-JUN alongside a B7-H3 CAR into the TRAC locus of primary human T cells utilizing CRISPR-Cas9. Non-viral c-JUN+B7-H3 CAR T cells show enhanced "],"journal":["Cell reports. Medicine"],"pubmed_title":["c-JUN enhances CRISPR knockin anti-B7-H3 CAR T cell function in small cell lung cancer and thoracic SMARCA4-deficient undifferentiated tumors."],"pmcid":["PMC12866126"],"funding_grant_id":["555464052","R35 CA283888","CAP36","R35CA283888"],"pubmed_authors":["George J","Tunuguntla R","Huang J","Balke-Want H","Asano K","Jiang Q","Liu X","Fowler C","Patel S","Mackall CL","Chen Y","Sage J","Klysz DD","Retherford A","Xu P","Del Carmen Arenas M","Feldman SA","Gkitsas-Long N","Keerthi V","Ho K","Ullrich R","Heitzeneder S","Sotillo E","Stahl D","Malipatlolla M","Maas L"],"additional_accession":[]},"is_claimable":false,"name":"c-JUN enhances CRISPR knockin anti-B7-H3 CAR T cell function in small cell lung cancer and thoracic SMARCA4-deficient undifferentiated tumors.","description":"Small cell lung cancer (SCLC), a highly lethal disease, limits T cell responses by downregulating major histocompatibility (MHC) class I molecules. Because chimeric antigen receptor (CAR) T cells are not MHC restricted, they may provide a powerful strategy against SCLC. However, few CAR targets for SCLC are known. Here, we show that B7-H3/CD276 is expressed in SCLC and thoracic SMARCA4-deficient undifferentiated tumors (UTs) that can clinicopathologically mimic SCLC. Thoracic SMARCA4-deficient UTs limit killing by B7-H3 CAR T cells via secretion of transforming growth factor β1 (TGF-β1). To overcome tumor-driven CAR T cell suppression, we knock in c-JUN alongside a B7-H3 CAR into the TRAC locus of primary human T cells utilizing CRISPR-Cas9. Non-viral c-JUN+B7-H3 CAR T cells show enhanced ","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-07-15T06:17:38.157Z","creation":"2026-06-30T03:21:47.41Z"},"accession":"S-EPMC12866126","cross_references":{"pubmed":["41564857"],"doi":["10.1016/j.xcrm.2025.102549"]}}