Figure 4
WT1-28z/IL-12 CAR T cells eradicates established tumors in a human xenograft mouse models. (a) SCID/Beige mice were injected i.v. with 5E6 Set2 cells and treated with i.v. injection of 2E7 CAR-positive primary human T cells 7 days post-tumor injection. WT1-28z CAR T cells significantly improved survival of mice compared to untreated mice (*P=0.006) or mice treated with control 4H11-28z CAR T cells (*P=0.01). WT1-28z/IL-12 CAR T cells had significant survival over mice treated with 4H11-28z/IL-12 CAR T cells (*P=0.004). (n=3 separate experiments). (b) SCID/Beige mice were i.v. injected with 5E6 Set2 cells and treated with i.v. injection of 2E7 CAR-positive primary human T cells 14 days post-tumor injection. WT1-28z/IL-12 CAR T cells significantly enhanced survival of mice in a more established disease model compared with WT1-28z CAR T cells (*P=0.006). (c) SCID/Beige mice were i.p. injected with 1E7 OVCAR3 cells and treated 41 days post-tumor injection with i.p. injection of 5E6 CAR-positive primary human T cells. WT1-28z CAR T cells mediated significantly enhanced survival compared with treatment with control 19-28z CAR T cells (*P=0.009) or untreated mice (*P=0.0034). A single dose of WT1-28z/IL-12 CAR T cells mediated significantly enhanced survival compared with treatment with control 19-28z/IL-12 CAR T cells (*P⩽0.0001). Mice treated with WT1-28z/IL-12 CAR T cells exhibited enhanced survival as compared with WT1-28z CAR T cells, but this difference was not statistically significant (P=0.23) (n=2 independent experiments). (d) Bioluminescent imaging of mice on day 58 after OVCAR3 tumor injection show eradication of tumor in mice treated with WT1-28z or WT1-28z/IL-12 CAR T cells.
