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| Home > Publications database > A comparative analysis of CD70-directed CAR-T cells for glioblastoma treatment demonstrates a superior efficacy of the ligand-based construct |
| Home > Publications database > A comparative analysis of CD70-directed CAR-T cells for glioblastoma treatment demonstrates a superior efficacy of the ligand-based construct |
| Journal Article | DKFZ-2026-00339 |
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2026
Elsevier
[New York]
Abstract: CD70, a member of the tumor necrosis factor receptor superfamily, is expressed in glioblastoma (GB), where it promotes tumor growth, migration, and immunosuppression.Accordingly, it has emerged as a target for chimeric antigenreceptor (CAR)-T cell therapy. Despite the influence of CARstructure on therapeutic efficacy, no comparative studieshave evaluated different CD70-directed CAR designs inGB. Our study addressed this gap. We first validatedCD70 expression in transcriptomic datasets, patient tissue,and GB cell lines. We then generated CD70-specificCAR-T cells featuring distinct target recognition and costimulatory domains (CD27z, LF28z, and LFBBz) andperformed phenotypic characterization. Using co-culturesystems and 3D cerebral organoids, we showed that all constructs eliminated target cells in a CD70-dependentmanner, with CD27z secreting the highest levels of Th1 cytokines. This functional advantage translated into superiorsurvival in an orthotopic GB mouse model. Based on thesefindings, we developed a panel of murine CD27-based constructs, all of which demonstrated potent antitumor activityin vitro and in immunocompetent GB mouse models,further underscoring the therapeutic promise of CD27 integration into the CAR design. Collectively, our comparativeanalysis highlights the superior efficacy of the ligand-basedconstruct, supporting its incorporation into a clinical trialtargeting CD70 in recurrent GB.
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