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. 2021 Jan 18;9(1):e001688. doi: 10.1136/jitc-2020-001688

Figure 4.

Figure 4

Depletion of Cbl-b inhibits CAR T-cell exhaustion and promotes tumor regression. (A) Schematic representation of the CEA-reactive CAR construct. (B) 6×106 cbl-b+/+ and cbl-b–/– CAR T cells were adoptively transferred into Rag–/– mice (n=6) on days 3 and 8 after tumor inoculation. Percentage survival of Rag–/– mice that received cbl-b+/+ and cbl-b–/– CAR T cells. The mice were considered dead when tumor size became 15 mm. Log-rank test was used for statistical analysis. (C) Tumor volume is shown; (D) sorted cbl-b+/+ and cbl-b–/– CD8+PD1+Tim3+ TILs were cocultured with MC38-CEA cells (target) labeled with calcein-AM. Specific lysis and expression of IFN-γ, TNF-α and granzyme B are shown. (E) Representative images of spleen and H&E-stained sections of the colon, lung and liver. The data are representative of three independent experiments. Statistics are mean±SD, calculated by Student’s t-test (two-tailed). AM, acetoxymethyl; CAR, chimeric antigen receptor; CEA, carcinoembryonic antigen; hCEA, human carcinoembryonic antigen; IFN-γ, intergeron gamma; scFv, single-chain variable fragment; TIL, tumor-infiltrating lymphocyte; TNF-α, tumor necrosis factor alpha.