Fig. 5 | Cancer Gene Therapy

Fig. 5

From: T-bet promotes potent antitumor activity of CD4+ CAR T cells

Fig. 5

CD4+ CAR T cells expressing T-bet (∆TBOX) promotes survival against lymphoma-bearing mice. a Schematic of in vivo RMA-B7H6 lymphoma model. C57Bl/6 mice were injected with (1 × 105) RMA-B7H6 intravenously (IV). Mice were then administered transduced T cells IV, 7 days post-tumor injection. Each mouse received 2.5 × 106 ConA-stimulated CAR T cells with 5 × 106 CD4+ purified Mock, B7H6-specific CAR, or B7H6-specific CAR/T-bet (TBOX) T cells (7.5 × 106 T cells total). Mice were monitored for 40 days post-tumor injection. b In vitro IFN-γ production of transduced T cells before pooling for experiment. CD4+ Mock T cells, CD4+ B7H6-specific CAR T cells, CD4+ B7H6-specific CAR/T-bet (TBOX) T cells, or ConA-stimulated CAR T cells were co-cultured with RMA or RMA-B7H6 for 24 h at an E:T of 1:1. ANOVA Dunnett’s test (*p < 0.05, **p < 0.01, ***p < 0.001). The data shown are representative of two independent experiments. c Kaplan–Meier survival curve of RMA-B7H6 bearing mice treated with CAR T cells (n = 12 per group). Treatment groups as described in a: CD4+ Mock T cells + ConA-stimulated T cells, CD4+ B7H6-specific CAR T cells + ConA-stimulated T cells, CD4+ B7H6-specific CAR/T-bet (TBOX) + ConA-stimulated T cells. Data are combined from two independent experiments. Log-rank Mantel–Cox test (***p < 0.001 B7H6-specific CAR/TBET (TBOX) vs Mock)

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