Figure 6. Combination therapy with trametinib and ALT-803 can drive rejection of Kras-mutated breast tumors.

(A) Brpkp110 cells were treated in vitro with vehicle, 8 nM, or 200 nM trametinib for 18 hr and analyzed by Western blot. (B) Mice were injected with Brpkp110 cells subcutaneously (day 0) and gavaged once daily with trametinib (1.0 mg/kg) on days 3–13. ALT-803 (0.2 mg/kg) was administered i.p. on days 3, 8, and 13. Tumor growth data from one of three experiments is shown, n=4 for Vehicle and Vehicle+ALT-803 groups; n=12 for Trametinib and Trametinib+ALT-803 groups. *P <0.05, Mann-Whitney test. (C) Plots showing growth of individual tumors from all mice in three experiments from (B). n=12 for Vehicle and Vehicle +ALT-803 groups; n = 27 for Trametinib and Trametinib+ALT-803 groups. (D) Percentage of mice with tumors <100 mm³ from (C) is plotted. *Trametinib+ALT-803 is significant from all other curves and Trametinib is significant from Vehicle, P <0.05, log-rank test. (E) Mice that rejected tumors from (C) were rechallenged >30 days later with Brpkp110 cells contralaterally and tumor growth was compared to cells injected into naive mice.