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. Author manuscript; available in PMC: 2022 Feb 4.
Published in final edited form as: Nat Med. 2020 Apr 27;26(5):720–731. doi: 10.1038/s41591-020-0827-2

Figure 6. Combined azacytidine and CAR T-cell therapy improves progression-free survival in PFA ependymoma orthotopic xenograft models.

Figure 6.

(a) Experimental scheme - PFA ependymoma cells expressing eGFP-firefly luciferase (PDX-GFP-Luc) were xenografted into NSG mice; 1-week post xenograft mice began subcutaneous treatment of azacytidine. Following BLI to determine engraftment, HER2 CAR-T-cells, TRI CAR-T-cells or non-transduced T-cells were intraventricularly administered by the lateral ventricle. Tumour burden was monitored weekly by BLI until endpoint. (b) Survival analysis of combined azacytidine and T-cell treated orthotopic xenografts of MDT-PFA4, MDT-PFA5 and Ep612. Two-sided log rank test (BH), n = 12 non-transduced T-cells plus azacytidine, 23 TRI CAR-T-cells + azacytidine, and 18 HER2 CAR-T-cells + azacytidine across 3 independent PDX models. MDT-PFA4: HER2-azacytidine vs HER2 P=0.0017, HER2-azacytidine vs T-cells P=0.00305, HER2-azacytidine vs T-cells-azacytidine P=0.00110, HER2-azacytidine vs TRI P=0.99, HER2-azacytidine vs TRI-azacytidine P=0.00011, TRI-azacytidine vs HER2 P=0.00029, TRI-azacytidine vs T-cells P=0.00061, TRI-azacytidine vs T-cells-azacytidine P=0.00025, TRI-azacytidine vs TRI P=0.00029. MDT-PFA5: HER2-azacytidine vs HER2 P=0.008, HER2-azacytidine vs T-cells P=0.011, HER2-azacytidine vs T-cells-azacytidine P=0.008, HER2-azacytidine vs TRI P=0.542, HER2-azacytidine vs TRI-azacytidine P=0.874, TRI-azacytidine vs HER2 P=0.008, TRI-azacytidine vs T-cells P=0.008, TRI-azacytidine vs T-cells-azacytidine P=0.008, TRI-azacytidine vs TRI P=0.737. Ep612: HER2-azacytidine vs HER2 P=0.84, HER2-azacytidine vs NT P=0.007, HER2-azacytidine vs T-cells P=0.00622, HER2-azacytidine vs T-cells-azacytidine P=0.00622, HER2-azacytidine vs TRI P=0.00622, HER2-azacytidine vs TRI-azacytidine P=0.00723, TRI-azacytidine vs HER2 P=0.00622, TRI-azacytidine vs NT P=0.0082, TRI-azacytidine vs T-cells P=0.00071, TRI-azacytidine vs T-cells-azacytidine P=0.00071, TRI-azacytidine vs TRI P=0.00071. (c) BLI and H&E staining analysis of NSG mice xenografted with Ep612, treated with azacytidine and intraventricularly infused with non-transduced T-cells, HER2 CAR-T-cells, or TRI CAR-T-cells (colour map indicates radiance), n = 5 HER2-azacytidine, 6 TRI-azacytidine, and 4 T-cells-azacytidine biologically independent PDX models. Each column represents one mouse, each row represents a time point, mouse endpoint (days post therapy) noted in ‘Days’.