Figure 2.
Maximal antitumor effect of elotuzumab requires both FcR-expressing NK cells and CD8+T cells in mouse tumor models. (A) BALB/c mice were injected subcutaneously with A20-hSLAMF7 tumor cells (10 × 106 cells) and randomized at day 11 when their tumors reached an average size of 180 ± 60 mm3. Mice were injected intraperitoneally with 10 mg/kg of either control mIgG2a (circles) or elotuzumab-g2a (triangles) on days 11, 14, and 18. n = 12 mice per group. *P = .022 vs IgG2a, day 21. (B-C) A20-hSLAMF7–bearing BALB/c mice were first randomized on day 7 (average tumor size: 117 ± 44 mm3) to receive anti-CD8α or anti–asialo-GM1 (days 7, 14, and 21) and then randomized again on day 10 (average tumor size: 166 ± 59 mm3) to receive 10 mg/kg of either control IgG2a or elotuzumab-g2a (days 10, 13, and 17) mAb. n = 10 mice per group. **P = .002 for elotuzumab-g2a/anti–asialo-GM1 vs elotuzumab-g2a; ***P = .0008 for elotuzumab-g2a/anti-CD8α vs elotuzumab-g2a, day 20. (D) C57BL/6 mice were injected subcutaneously with EG7-hSLAMF7 tumor cells (5 × 106 cells) and randomized on day 7 when their tumors reached an average size of 98.9 ± 9.6 mm3. Mice were injected intraperitoneally with 10 mg/kg of either control IgG2a (circles) or elotuzumab-g2a (triangles) on days 7, 11, and 14. n = 7-8 mice per group. *P = .04 vs IgG2a, day 25; and P = .03 vs IgG2a, day 27. (E) EG7-hSLAMF7–bearing C57BL/6 mice were randomized on day 7 (average tumor size: 82 ± 42 mm3) to receive 10 mg/kg of control IgG2a (circles), elotuzumab-g2a (triangles), or elotuzumab–mg1-D265A (inverted triangles) on days 7, 11, and 14. n = 10-11 mice per group. *P = .04 elotuzumab-g2a vs control IgG2a, day 18. Data are mean ± SEM. Statistical analyses were performed at the indicated time point using the Mann-Whitney U test.