Figure 3.
Elotuzumab-g2a and anti–PD-1 mAbs show synergistic antitumor activity. (A) Splenocytes and tumor-infiltrating lymphocytes from A20-hSLAMF7– or EG7-hSLAMF7–bearing mice were harvested. The proportion of splenic or tumor-infiltrating CD4+CD3+, CD8+CD3+, or NKp46+CD3− cells that expressed PD-1 was quantified. Results are a composite of 3 independent experiments with a total of 5 to 22 mice per group; error bars show SEM. Frequencies of tumor-infiltrating vs splenic PD-1+ cells were compared by using the paired Student t test. (B) A20-hSLAMF7 and EG7-hSLAMF7 cells prior to implantation were stained with either isotype control (filled red histogram) or anti-mouse PD-L1 (mPD-L1; blue histogram). A flow cytometry histogram representative of PD-L1 expression is shown. (C-D) A20-hSLAMF7–bearing mice were randomized to different treatment groups on day 10 when their tumors reached an average size of 157 ± 63 mm3 and were treated with 10 mg/kg elotuzumab-g2a or control mIgG2a and/or 3 mg/kg anti–PD-1 injected intraperitoneally on days 10, 14, and 17. Tumor volumes for individual mice (C) and percent survival (D) are shown. n = 9 per group. Differences between survival curves were analyzed by using the Mantel-Cox test. (E) EG7-hSLAMF7–bearing mice were randomized to different treatment groups on day 7 when their tumors reached an average size of 120 ± 51 mm3 and were treated with 10 mg/kg elotuzumab-g2a or control mIgG2a and/or 10 mg/kg anti–PD-1 injected intraperitoneally on days 7, 10, and 14. Tumor volumes for individual mice and the number of tumor-free mice per group are shown. n = 9 per group. **P < .01; ***P < .0001.