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. 2023 Feb 17;210(7):991–1003. doi: 10.4049/jimmunol.2200646

FIGURE 7.

FIGURE 7.

cIAP1/2 antagonism combines with adoptive T cell therapy and induces 4-1BB expression in vivo. (A) B16-OVA cells (2 × 106) were implanted s.c. in C57BL/6 mice or TCRα−/− mice. Mice were dosed with 75 mg/kg LCL-161 by oral gavage every 3 d starting on day 1 postimplantation. Tumor volumes were measured by precision calipers. (B) CD8 T cells were isolated from a TRP1high mouse and activated in vitro for 48 h with anti-CD3/CD28 and vehicle or 500 nM LCL-161. CD8 T cells were washed and adoptively transferred into C57BL/6 mice that had been s.c. inoculated with 250,000 B16-F10 melanoma cells 5 d prior to T cell transfer. Mice were also treated with vehicle or LCL-161 (75 mg/kg) by oral gavage every 3 d starting on day 5. n = 5 per group. Vehicle, no T cells, vehicle oral gavage; TRP1 T cells, vehicle-treated TRP1 cells, vehicle oral gavage; LCL-161, no T cells, LCL-161 oral gavage; TRP1 T cells + LCL-161, LCL-161 treated TRP1 cells, LCL-161 oral gavage. (C) C57BL/6 mice were inoculated s.c. with 300,000 C2VTRP1 cells. On day 7, some mice received adoptive transfer of naive TRP1high;CD45.1+ CD8 T cells as indicated. Mice were also treated with vehicle or 75 mg/kg LCL-161 by oral gavage every 2 d starting on day 7. Tumor volumes were measured over time. (D) Flow cytometry analysis of 4-1BB expression on activated peripheral blood CD8 T cells from mice in (C). Gating strategy is shown in Supplemental Fig. 4. Endo, endogenous T cells (CD45.1−). Error bars are SEM throughout.