Anti-Human IGF1 Receptor Recombinant Antibody (Robatumumab) (CAT#: TAB-209)

Figure 1 SCH 717454 downregulates IGF-IR and inhibits both basal and IGF-I–induced phosphorylation of IGF-IR and IRS-1 in pediatric tumor lines.

A, SK-N-FI cells either untreated or treated with control IgG1 (lane 2; 80 nmol/L) or various concentrations of SCH 717454 (0.2-80 nmol/L) for 0.5 or 4 h before stimulation with IGF-I (50 ng/mL) for 10 min. Cell lysates were subjected to Western analysis and probed with phosphorylated IGF-IR–specific antibody (top). The filter was then reprobed with an antibody that recognizes total IGF-IR. For the 4 h time point, the same blot was stripped and reprobed with anti-actin antibody as loading control. B, SK-N-FI cells were either untreated or treated with control IgG1 (lane 2; 80 nmol/L) or various concentrations of SCH 717454 (0.2-80 nmol/L) for 0.5 h before stimulation with IGF-I (50 ng/mL) for 10 min. Cell lysates were probed with anti-phosphorylated IRS-1 antibody (pY612). C, various pediatric tumor cell lines were either untreated (control; lane 1) or treated with SCH 717454 (20 nmol/L, 4 h; lane 2) or IGF-I (100 ng/mL, 20 min; lane 3). Cell lysates were then probed with anti-phosphorylated IRS-1 antibody (pY612). The blots were stripped and reprobed with anti-total IRS-1 antibody.

Wang, Y., Lipari, P., Wang, X., Hailey, J., Liang, L., Ramos, R., ... & Wang, Y. (2010). A fully human insulin-like growth factor-I receptor antibody SCH 717454 (Robatumumab) has antitumor activity as a single agent and in combination with cytotoxics in pediatric tumor xenografts. Molecular cancer therapeutics, 1535-7163.

Figure 2 SCH 717454 inhibits pediatric tumor growth in xenograft models as a single agent and in combination with chemotherapeutic agents.

A and B, nude mice were inoculated s.c. with SK-N-FI neuroblastoma cells (5 × 106 per mouse). When the average tumor size reached 150 mm3 (on day 21 post-inoculation), tumor-bearing mice were randomized to indicated treatment groups (10 mice per group) and treatments (i.p. route) with either 0.1 mg control IgG1 antibody, 0.04 mg or 0.1 mg SCH 717454 (twice weekly), 100 mg/kg cyclophosphamide (once weekly), 2 mg/kg cisplatin (twice weekly), or both SCH 717454 and cyclophosphamide were initiated. C, nude mice were inoculated s.c. with SJSA-1 osteosarcoma cells (7 × 106 per mouse). When tumor size reached 96 mm3, mice randomized to indicated treatment groups (10 per group) were treated i.p. (twice weekly) with either control IgG1 antibody, SCH 717454, 100 mg/kg cyclophosphamide, or both SCH 717454 and cyclophosphamide. Note that cyclophosphamide dosing ceased after three doses, whereas SCH 717454 dosing continued until the tumor volume reached 1,000 mm3. D, effects of SCH 717454 on RD rhabdomyosarcoma xenograft growth as a single agent and in combination with cyclophosphamide. Nude mice were inoculated s.c. with RD rhabdomyosarcoma cells (7 × 106 per mouse). Treatment (i.p. twice weekly for 0.5 mg control IgG1, 0.1 and 0.5 mg SCH 717454, and 100 mg/kg cyclophosphamide) was initiated when the average tumor size reached 125 mm3. On day 18 after the treatment initiation, when control group tumor volume reached 660 mm3, the study was terminated and tumor growth inhibition or regression in various groups was calculated. Bars, SE. *, P< 0.05, compared with IgG1 control; #,P< 0.05, compared with single treatments.

Wang, Y., Lipari, P., Wang, X., Hailey, J., Liang, L., Ramos, R., ... & Wang, Y. (2010). A fully human insulin-like growth factor-I receptor antibody SCH 717454 (Robatumumab) has antitumor activity as a single agent and in combination with cytotoxics in pediatric tumor xenografts. Molecular cancer therapeutics, 1535-7163.

Figure 3 SCH 717454 inhibits tumor expression of Ki-67 in vivo.

A, SK-N-FI neuroblastoma xenograft tumors were collected and analyzed by Ki-67 immunostaining and H&E staining on twice weekly treatment with 0.1 mg SCH 717454 for 2 wk. B, SJSA-1 osteosarcoma xenograft tumors were collected 3 d after a single treatment of SCH 717454. Average tumor size at the time of treatment was 155 and 130 mm3 for SK-N-FI and SJSA-1 xenografts, respectively. Tumor proliferation status was assessed with anti–Ki-67 antibody by immunohistochemistry. Tissue sections were counterstained with hematoxylin.

Wang, Y., Lipari, P., Wang, X., Hailey, J., Liang, L., Ramos, R., ... & Wang, Y. (2010). A fully human insulin-like growth factor-I receptor antibody SCH 717454 (Robatumumab) has antitumor activity as a single agent and in combination with cytotoxics in pediatric tumor xenografts. Molecular cancer therapeutics, 1535-7163.