Fig. 4: Locoregional intracerebroventricular delivery of HER2-CAR/mbIL12 T cells reduces tumor burden and increases regional and systemic CAR T-cell persistence in vivo.
From: Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting
a Schematic for intratibial (i.ti.) and intracranial (i.c.) BBM1 dual-tumor model and treatment. b Representative bioluminescent flux imaging of dual-tumor-bearing mice left untreated (no tx), or treated by intracerebroventricular (i.c.v.) injection of HER2-CAR or HER2-CAR/mbIL12 T cells. c Quantification of brain (top) or bone (bottom) flux from individual mice treated i.c.v. with HER2-CAR T cells (n = 11/group), HER2-CAR/mbIL12 T cells (n = 11/group), or no tx (n = 4/group). P < 0.05 for bone flux, and not significant (ns) for brain flux, comparing HER2-CAR and HER2-CAR/mbIL12 using a Multiple Mann–Whitney test. d, e Representative flow cytometric analysis (d) and quantification (e) of HER2-CAR T cells per µL of blood at weeks 1, 2, and 5 post-treatment. e n = 11–12/group. Data are presented as mean values ±SEM. P values indicate differences between HER2-CAR and HER2-CAR/mbIL12 using a two-tailed Student’s t test. f Immunohistochemistry of CD3+ T cells in i.ti. and i.c. tumors at day 7 post-treatment. Data are representative of n = 3 mice/group. Scale bar = 100 µm.
