Extended Data Fig. 10: Activation of CAR T cells - in vivo potency trial.
a, Heatmap of the normalized Z-scores of Human cytokines associated with T cell activation and augmentation, present in the blood circulation and CSF of NSG mice, in response to 2.5×106, 5.0×106 and 10×106 EPHA2 CAR T cells, TRI CAR T cells, or non-transduced T cells; delivered intraventricularly via the lateral ventricle, or IV via the tail vein. N = 36 EPHA2 (n = 16 blood and 16 CSF independent animal samples; n = 9 lateral ventricle and 9 intravenous CARs or T-cell infusions; n = 3 2.5×106, 3 5.0×106 and 3 10×106 CAR T-cell or non-transduced T-cell infusions., Samples were harvested 8 weeks post therapy, or at humane endpoint. b, IHC analysis of EPHA2 CAR T cell accumulation in mice treated within the associated in vivo potency trial, as indicated by CD3-positive protein expression. Top panel denotes mice infused IV with a dose range of 2.5×106, 5.0×106 and 10×106 EPHA2 CAR T cells, the bottom panel denotes mice infused intraventricularly via the lateral ventricle with a dose range of 2.5×106, 5.0×106 and 10×106 EPHA2 CAR T cells. Red arrows indicate EPHA2 T cell infiltration. Results representative of 2 independent replicates. c, IHC analysis of EPHA2 CAR T cell accumulation from archival FFPE samples of trial treated mice. The top panel denotes mice infused with non-transduced T cells, the bottom panel indicates mice treated with EPHA2 CAR T cells either intravenously (left), intraventricularly by the lateral ventricle (LV) (middle) or LV combined with Azacytidine (right) with a dose range of 5.0×106. Results representative of 2 independent replicates, red arrows indicate EPHA2 T cell infiltration.
