Figure 5. Enhancement of antitumor activity of cetuximab by anti-CD137 mAb is dependent on NK and CD8+ T cells.
BALB/c mice were inoculated with 1 × 106 TUBO-EGFR tumor cells s.c. (A, schema). Mice (10 per group) then received either rat IgG on day 14 (circles), cetuximab on day 14 (squares), anti-CD137 antibody on day 15 (diamonds), or cetuximab on day 14 and anti-CD137 antibody on day 15 (triangles), each repeated 4 times weekly, with animals monitored for tumor growth (B, *P = 0.047) and overall survival (C, *P < 0.001). After tumor inoculation, mice (10 per group) received either rat IgG on day 14 (circles) or cetuximab on day 14 and anti-CD137 antibody on day 15, with each injection repeated weekly for a total of 4 injections with anti–asialo-GM1 starting on day –1 (diamonds), liposomal clodronate starting on day –2 (upside-down triangles), anti-CD8 mAb starting on day –1 (squares), anti-CD4 mAb starting on day –1 (red circles), or no cell-depleting mAb (blue triangles); animals were monitored for tumor growth (D, *P < 0.001; **P < 0.008) and overall survival (E, *P < 0.001). Naive BALB/c mice were inoculated with 1 × 106 TUBO-EGFR (circles) or 1 × 106 TUBO tumor cells (upside-down triangles), or BALB/c mice previously (100 days prior) inoculated with TUBO-EGFR tumor cells and cured with cetuximab and anti-CD137 antibody were inoculated with 1 × 106 TUBO-EGFR (blue triangles) or 1 × 106 TUBO tumor cells (red squares) s.c. and monitored for tumor growth (F, *P < 0.001) and overall survival (G, *P < 0.001).