biostudies-literatureBrown CENational Cancer InstituteNCI NIH HHSNational Institutes of HealthCalifornia Institute of Regenerative Medicine1318-1330https://www.ebi.ac.uk/biostudies/studies/S-EPMC9340633biostudies-literatureUnknown24(8)<h4>Background</h4>Wide-spread application of chimeric antigen receptor (CAR) T cell therapy for cancer is limited by the current use of autologous CAR T cells necessitating the manufacture of individualized therapeutic products for each patient. To address this challenge, we have generated an off-the-shelf, allogeneic CAR T cell product for the treatment of glioblastoma (GBM), and present here the feasibility, safety, and therapeutic potential of this approach.<h4>Methods</h4>We generated for clinical use a healthy-donor derived IL13Rα2-targeted CAR+ (IL13-zetakine+) cytolytic T-lymphocyte (CTL) product genetically engineered using zinc finger nucleases (ZFNs) to permanently disrupt the glucocorticoid receptor (GR) (GRm13Z40-2) and endow resistance to glucocorticoid treatment. In a phase Neuro-oncologyOff-the-shelf, steroid-resistant, IL13Rα2-specific CAR T cells for treatment of glioblastoma.PMC9340633R01CA254271P30 CA033572R01 CA236500R01 CA254271P30CA033572CLIN2-10248R01CA236500R01CA155769R01 CA155769Ostberg JRWagner JRHolmes MCJensen MCNaranjo ATran VWeng LZhou YRodriguez AForman SJBadie BBrown CEStarr RSynold TWGregory PDTang WWD'Apuzzo MWang SMendel MRessler JAAguilar BReik APalmer JfalseOff-the-shelf, steroid-resistant, IL13Rα2-specific CAR T cells for treatment of glioblastoma.<h4>Background</h4>Wide-spread application of chimeric antigen receptor (CAR) T cell therapy for cancer is limited by the current use of autologous CAR T cells necessitating the manufacture of individualized therapeutic products for each patient. To address this challenge, we have generated an off-the-shelf, allogeneic CAR T cell product for the treatment of glioblastoma (GBM), and present here the feasibility, safety, and therapeutic potential of this approach.<h4>Methods</h4>We generated for clinical use a healthy-donor derived IL13Rα2-targeted CAR+ (IL13-zetakine+) cytolytic T-lymphocyte (CTL) product genetically engineered using zinc finger nucleases (ZFNs) to permanently disrupt the glucocorticoid receptor (GR) (GRm13Z40-2) and endow resistance to glucocorticoid treatment. In a phase 2022-01-01T00:00:00Z2022 Aug2026-05-09T22:21:52.169Z2024-11-19T19:15:35.25ZS-EPMC93406333510037310.1093/neuonc/noac024