CAR T cells targeting the glycoprotein GD2 show potent antitumor efficacy in high-risk ependymoma models
Antonio Carlos Tallon-Cobos, Konstantinos Vazaios, Piotr Waranecki, Marliek van Hoesel, Annelisa Cornel, Benjamin Schwalm, Norman Mack, Ella de Boed, Jasper van der Lugt, Stefan Nierkens, Marcel Kool, Eelco W. Hoving, Dennis S. Metselaar, Esther Hulleman
Antonio Carlos Tallon-Cobos, Konstantinos Vazaios, Piotr Waranecki, Marliek van Hoesel, Annelisa Cornel, Benjamin Schwalm, Norman Mack, Ella de Boed, Jasper van der Lugt, Stefan Nierkens, Marcel Kool, Eelco W. Hoving, Dennis S. Metselaar, Esther Hulleman
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Research Letter Immunology Neuroscience Oncology

CAR T cells targeting the glycoprotein GD2 show potent antitumor efficacy in high-risk ependymoma models

Abstract

Authors

Antonio Carlos Tallon-Cobos, Konstantinos Vazaios, Piotr Waranecki, Marliek van Hoesel, Annelisa Cornel, Benjamin Schwalm, Norman Mack, Ella de Boed, Jasper van der Lugt, Stefan Nierkens, Marcel Kool, Eelco W. Hoving, Dennis S. Metselaar, Esther Hulleman

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Figure 1

High-risk EPN models present the immunotherapeutic target GD2 and are sensitive to GD2–CAR T cell therapy in vitro and in vivo.

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High-risk EPN models present the immunotherapeutic target GD2 and are se...
(A) Immunofluorescence images of GD2 expression across 7 high-risk EPN models versus a GD2 negative control (VUMC-ATRT-03). Highlighted boxes indicate a higher objective (×63) of the indicated area (×20). Scale bars: 100 μm for ×20 objective and 25 μm for ×63 objective, respectively. (B) Representative flow cytometry histogram of GD2 membrane expression across all EPN models, 2 DMG positive controls (HSJD-DIPG-07 and VUMC-DIPG-G) and 2 negative controls (VUMC-DIPG-10 and VUMC-ATRT-03). The experiment was performed 3 times. (C) Schematic for the EPN-GD2–CAR T cell coculture. (D) Left: Killing curves showing GD2–CAR T cells mediating potent dose-dependent lysis in ST-ZFTA-RELA EPN (upper) and PF-A EPN (lower). Right: GD2–CAR T cells show significantly higher tumor killing than untransduced matched donor T cell controls. Each dot represents the average of 3 technical replicates over 3 independent repetitions. (E) Left: GD2–CAR T cells mediate potent IFN-γ secretion when presented with ST-ZFTA-RELA-EPN and PF-A EPN models, but not with a GD2 negative control (VUMC-ATRT-03). Right: GD2–CAR T cells show significantly higher IFN-γ secretion compared with untransduced matched donor T cell controls. Each dot represents the average of 3 technical replicates over 3 independent repetitions of the experiment. (F) Schematic for the in vivo experiments. (G) Tumor BLI signal over time of the medium tumor burden. (H) Kaplan-Meier survival curves of the mice with the starting higher tumor burden. In all experiments, *P <.05, **P <.01, ***P <.005, and ****P <.001, by multiple unpaired, 2-tailed Student’s t test (D and E, right) and 2-way ANOVA (E, left). Data represent the mean ± SD.