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Chimeric antigen receptor T\u2010cell (CAR\u2010T) therapy has shown promising results in liquid malignancies, but clinical trials in GBM targeting various tumor antigens have not shown durable clinical benefit. While this may be attributable to various tumor\u2010intrinsic immune evasion strategies characteristic of GBM, little work has been done to assess whether the issue is due to the quality of the CAR\u2010T treatment itself. Currently, CAR\u2010Ts for GBMs and liquid malignancies are manufactured in an autologous setting in which T\u2010cells are extracted from patients, engineered ex\u00a0vivo, and subsequently reinfused back. However, peripheral T\u2010cells taken from untreated GBM patients have demonstrated qualitative and functional deficits, which may contribute to suboptimal treatment outcomes. Thus, we aimed to establish whether CAR\u2010Ts generated from GBM patients would show reduced efficacy in comparison to healthy donors using our previously validated CD133 CAR\u2010T. In this work, we show pre\u2010treatment exhaustion and reduced survival advantage in autologous, patient\u2010derived CD133\u2010targeting CAR\u2010T cell products using an orthotopic xenograft model of human GBM. To overcome the functional and logistical considerations of autologous therapy, we additionally aimed to generate an \u201coff\u2010the\u2010shelf\u201d allogeneic CD133 CAR\u2010T. Using CRISPR gene editing technology, we generated TCR\u2010knockout CAR\u2010T cells with comparable pre\u2010clinical efficacy to our autologous models. Ultimately, this work highlights the need to reassess autologous CAR\u2010T therapy for GBM and consider allogeneic approaches as biologically informed therapeutic alternatives.<\/jats:p>","DOI":"10.1002\/ijc.70509","type":"journal-article","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T02:59:48Z","timestamp":1777085988000},"page":"1521-1534","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Generation of Allogeneic\n                    <scp>CAR<\/scp>\n                    \u2010T Circumvents Functional Deficits in Patient\u2010Derived Autologous Product for Glioblastoma"],"prefix":"10.1002","volume":"159","author":[{"given":"Sabra K.","family":"Salim","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad 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