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. Author manuscript; available in PMC: 2021 Mar 25.
Published in final edited form as: Nat Med. 2020 Apr 27;26(5):712–719. doi: 10.1038/s41591-020-0821-8

Fig. 3 |. Locoregionally administered B7-H3 CAR T cells home more rapidly to cerebral ATRT xenografts than those administered intravenously. B7-H3 CAR T cells administered intracerebroventricularly efficiently migrate out of the CNS.

Fig. 3 |

a, Experimental setup (IT, ICV: 1 × 106 CAR T cells; IV: 10 × 106 CAR T cells). LTR, long terminal repeat. b, Bicistronic vector expressing NanoLuc luciferase and the CAR T cell fused to a fluorescent protein. c, BLI signal emanating from the CAR T cells was measured at the indicated time points. d, Quantification of BLI signal in the brain of mice on day 5 after treatment (n = 7 IT, n = 8 ICV and n = 5 IV B7-H3 CAR T cell-treated mice). IT versus ICV, P = 0.613; IT versus IV, *P = 0.048; ICV versus IV, *P = 0.011 (two-tailed Mann–Whitney U-test). Experiments were conducted in two independent cohorts of mice. e, Immunofluorescence microscopy imaging of brains from mice on day 2 after treatment. B7-H3 or control CD19 CAR T cells are shown in green in mice that were previously engrafted with BT16 ATRT cells (red). Tiled images across engrafted regions (top), representative confocal microscopy of B7-H3 CAR T cell-treated groups (middle) and CD19 - CAR T cell-treated groups (bottom) are shown. Scanning of 1:12 series from three independent mice per group. f,g, Quantification (f) and representative flow cytometry (g) showing persisting T cells in the brain following administration of 1 × 106 (IT and ICV) or 10 × 106 (IV) B7-H3 CAR T cells (n = 6 IT, n = 6 ICV and n = 6 IV B7-H3 CAR T cell-treated mice). Pooled data from two independent experiments (IT versus ICV, P = 0.394; IT versus IV, P = 0.732; ICV versus IV, P = 0.394). Two-tailed Mann–Whitney U-test. h, BLI 13 and 27 d after B7-H3 CAR T cell treatment. i, Quantification of BLI signal in the trunk of mice on day 27 after treatment (IT versus ICV, *P = 0.026; IT versus IV, P = 0.178; ICV versus IV, P = 0.329; n = 6 IT, n = 6 ICV and n = 5 IV B7-H3 CAR T cell-treated mice). Two-tailed Mann–Whitney U-test. All data shown are the mean ± s.e.m.