Figure 5.

BMS-986012 efficacy is enhanced by anti-CD137 antibody. A, BMS-986012 induces NK-cell activation in the presence of DMS79 target cells. Negatively selected human NK cells and DMS79 target cells were cocultured 1:1 for 24 hours in RPMI1640 plus 10% FBS without IL2 with serially diluted BMS-986012 or isotype control antibody. Expression of CD137 (left) and CD107a (middle) was determined by flow cytometry. IFNγ secreted into culture supernatants was determined by ELISA (right). Data are representative of three independent experiments. B, Mice were dosed every 3 to 4 days with 3 mg/kg BMS-986012 beginning on day 7 postimplantation or 1 mg/kg anti-mouse CD137 beginning day 8 posttransplantation to assess single-agent efficacy. To evaluate combined activity, mice were dosed with 3 mg/kg BMS-986012 every 3 to 4 days intraperitoneally beginning on day 7 after tumor implantation and either 0.1 or 0.3 mg/kg anti-mouse CD137 intraperitoneally 1 day after each dose of BMS-986012 beginning on day 8 post implantation. Data are representative of two independent experiments.