Figure 5.

Effect on lung metastases in tumor-bearing mice of combination treatment with bortezomib (Bzb) and death receptor (DR5) agonist antibody vs MD5-1 treatment with single agent. BALB/c wild-type (WT) mice bearing tumors derived from Renca-FLAG and 4T1 tumor cells were injected intravenously with Bzb (0.5 mg/kg) and/or MD5-1 (5 µg per mouse) on days 4, 7, 11, and 15 after tumor cells were injected (ie, day 0). Lung metastases counts are shown on day 18 following therapy. A) Renca-FLAG (5 × 10⁴) (n = 14 per treatment group; n = 21 in the untreated group). B) 4T1 (2 × 10⁴) (n = 10). *P < .001 (analysis of variance [ANOVA], two-sided) compared with other treatment groups. Data from three independent experiments are shown. C) Lung metastases counts are shown on day 18 after therapy in Renca- FLAG (5 × 10⁴) tumor–bearing BALB/c WT mice treated with the combination regimen (Combo) of Bzb (1 mg/kg) and MD5-1 (50 µg per mouse) or individual agents at the same or higher doses of Bzb (1.5 mg/kg) or MD5-1 (200 µg per mouse); n = 5 mice per group. *P = .004 (ANOVA, two-sided) when compared with all other treatment groups.