biostudies-literatureWickman ECure4CamNational Cancer InstituteAmerican Lebanese Syrian Associated CharitiesNINDS NIH HHSAlliance for Cancer Gene TherapyAlex Lemonade Stand Foundatione009743https://www.ebi.ac.uk/biostudies/studies/S-EPMC11580246biostudies-literatureUnknown12(11)<h4>Background</h4>Oncofetal splice variants of extracellular matrix (ECM) proteins present a unique group of target antigens for the immunotherapy of pediatric cancers. However, limited data is available if these splice variants can be targeted with T cells expressing chimeric antigen receptors (CARs).<h4>Methods</h4>To determine the expression of the oncofetal version of tenascin C (TNC) encoding the C domain (C.TNC) in pediatric brain and solid tumors, we used quantitative reverse transcription PCR and immunohistochemistry. Genetically modified T cells were generated from human peripheral blood mononuclear cells and evaluated in vitro and in vivo.<h4>Results</h4>We demonstrate that C.TNC is expressed on a protein level in pediatric tumors, including diffuse intrinsic pontine glioma, ostJournal for immunotherapy of cancerIL-18R supported CAR T cells targeting oncofetal tenascin C for the immunotherapy of pediatric sarcoma and brain tumors.PMC11580246P30CA021765N/AR01NS122859R01 NS122859F31CA250401-01A11F31CA257757R01NS121249Shaw TITian LPerry SSKrenciute GZhang JShanmugam RGottschalk SWagner JChiang JWickman EKoo SCBell MLu MSheppard HLange SIbanez JVogel PLangfitt DfalseIL-18R supported CAR T cells targeting oncofetal tenascin C for the immunotherapy of pediatric sarcoma and brain tumors.<h4>Background</h4>Oncofetal splice variants of extracellular matrix (ECM) proteins present a unique group of target antigens for the immunotherapy of pediatric cancers. However, limited data is available if these splice variants can be targeted with T cells expressing chimeric antigen receptors (CARs).<h4>Methods</h4>To determine the expression of the oncofetal version of tenascin C (TNC) encoding the C domain (C.TNC) in pediatric brain and solid tumors, we used quantitative reverse transcription PCR and immunohistochemistry. Genetically modified T cells were generated from human peripheral blood mononuclear cells and evaluated in vitro and in vivo.<h4>Results</h4>We demonstrate that C.TNC is expressed on a protein level in pediatric tumors, including diffuse intrinsic pontine glioma, ost2024-01-01T00:00:00Z2024 Nov2026-06-02T04:35:24.935Z2025-04-04T23:33:48.612ZS-EPMC115802463957215810.1136/jitc-2024-009743