Artikel
Characterisation of the heterogenous antigen-expression pattern in matched samples of primary and recurrent glioblastoma as a prerequisite for CAR-T cell engineering
Charakterisierung des heterogenen Antigenexpressionsmusters in Glioblastomen und ihren Rezidiven als Voraussetzung für das CAR-T Zell-Design
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Veröffentlicht: | 4. Juni 2021 |
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Gliederung
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Objective: Recent studies showed promising progress in the treatment of glioblastoma patients with CAR-T cells. Antigen escape mechanisms of malignant gliomas still constitute major obstacles and are reasons for non-response or relapse. Here, we present data for the surface expression of the ten in vitro and in vivo most targeted antigens in CAR-T cell therapy in primary and recurrent glioblastoma patients, their local distribution within the tumor and changes in relapse.
Methods: Tissue samples of 35 patients with glioblastomas and their respective relapses were analysed for expression of HER2, EGFRvIII, CD70, B7H3, Il13Rα2, NY-ESO1, GD2, CD133, CSPG4 and EphA2 by immunohistochemistry. In order to determine antigen expression in normal brain, slides of three healthy specimens (cerebrum, cerebellum, brain stem) were stained for the same antigens. To specify intrapersonal heterogeneity, five representative areas per patient and slide were evaluated.
Results: Interestingly, some antigens like EGFRvIII and NY-ESO1 showed a rather low expression in primary and recurrent glioblastoma while others like GD2, CD70, CD133 and EphA2 were expressed moderately. Three antigens were significantly increased in relapse relative to the tissue primarily obtained: HER2 (p=0.005, Cohen’s r=0.48), EGFRvIII (p=0.042, Cohen’s r=0.344), and GD2 (p=0.013, Cohen’s r=0.42). There were significant intrapersonal expression differences detectable for each antigen. However, none of the ten antigens was found in healthy brain tissue.
Conclusion: Thus, inter- and intrapersonal heterogeneity is one of the major obstacles to be overcome in order to implement targeted therapies for the treatment of glioblastoma.