Robatumumab

Robatumumab (Sch 717454) is an anti-human IGF-1R (insulin-like growth factor receptor-1) antibody. Robatumumab shows anti-tumor activity and anti-proliferative activity to cancer cells. Robatumumab can be used in osteosarcoma and Ewing sarcoma research[1][2].

Research Areas >> Cancer

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> IGF-1R

Robatumumab (0.02-80 nM; 0.5 or 4 h) downregulates IGF-IR and inhibits both basal and IGF-I-induced phosphorylation of IGF-IR and IRS-1 in SK-N-FI cells[2]. Western Blot Analysis[2] Cell Line: SK-N-FI cells Concentration: 0.02-80 nM Incubation Time: 0.5 or 4 hours Result: Inhibited the IGF-I–stimulated phosphorylation of IGF-IR after treatment 0.5 h. Resulted in both inhibition of IGF-IR phosphorylation and receptor downregulation after treatment 4 h. Resulted in a dose-dependent inhibition of the IGF-I–stimulated IRS-1 phosphorylation.

Robatumumab (intravenous injection; 0.04 or 0.1 mg/mouse; twice weekly; 18 d) inhibits the SK-N-FI tumor growth in xenograft model[2]. Robatumumab (intravenous injection; 0.02-0.5 mg/mouse; twice weekly; 35 d) inhibits the osteosarcoma growth in xenograft model[2]. Robatumumab (intravenous injection; 0.1 or 0.5 mg/mouse; twice weekly; 14 d) inhibits the SJCRH30 and RD rhabdomyosarcoma cell growth in xenograft model[2]. Robatumumab (intravenous injection; 0.1 or 0.5 mg/mouse; twice weekly; 2 w) blocks effectively pediatric tumor cell proliferation in vivo[2]. Robatumumab (intravenous injection; 0.5 mg/mouse; once; day 11 post-inoculation) modulates the blood vessel formation via its antiangiogenesis effect[2]. Animal Model: Nude mice inoculated with SK-N-FI tumor cells[2] Dosage: 0.04 or 0.1 mg/mouse Administration: Intravenous injection; 0.04 or 0.1 mg/mouse; twice weekly; 18 days Result: Inhibited the SK-N-FI xenograft tumor by 96% in the 0.04 mg dose group and resulted in 11% tumor regression in the 0.1 mg dose group. Animal Model: Nude mice inoculated with SJSA-1 osteosarcoma[2] Dosage: 0.02, 0.1 or 0.5 mg/mouse Administration: Intravenous injection; 0.02, 0.1 or 0.5 mg/mouse; twice weekly; 35 days Result: Inhibited the tumor growth by 71%, 82%, and 88% at 0.02, 0.1, and 0.5 mg, respectively, at day 14 after treatment. Animal Model: Nude mice inoculated with SJCRH30 and RD rhabdomyosarcoma cells[2] Dosage: 0.1 or 0.5 mg/mouse Administration: Intravenous injection; 0.1 or 0.5 mg/mouse; twice weekly; 14 days Result: Inhibited tumor growth by 39% and 58% at 0.1 and 0.5 mg dose, respectively, in the RD rhabdomyosarcoma model. Inhibited tumor growth by 37% and 53% at 0.1 and 1 mg dose, respectively, in the SJCRH30 model. Animal Model: Nude mice inoculated with SK-N-FI neuroblastoma and SJSA-1 osteosarcoma[2] Dosage: 0.1 or 0.5 mg/mouse Administration: Intravenous injection; 0.1 or 0.5 mg/mouse; twice weekly; 2 weeks Result: Reduced the tumor Ki-67 staining by 38% and along with significant change in SK-N-FI neuroblastoma xenograft. Reduced the staining of Ki-67 by 37% and 51% after 0.1 and 0.5 mg SCH 717454 treatment, respectively, in the SJSA-1 osteosarcoma xenograft. Animal Model: Nude mice inoculated with SJSA-1 osteosarcoma[2] Dosage: 0.5 mg/mouse Administration: Intravenous injection; 0.5 mg/mouse; once; day 11 post-inoculation Result: Reduced in the intensity of the fluorescent lectin staining by 74% at 0.5 mg dose, showing thinner blood vessels and reduced branches, compared with control IgG1.

[1]. Anderson PM, et al. A phase II study of clinical activity of SCH 717454 (robatumumab) in patients with relapsed osteosarcoma and Ewing sarcoma. Pediatr Blood Cancer. 2016 Oct;63(10):1761-70.

[2]. Wang Y, et al. 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. Mol Cancer Ther. 2010 Feb;9(2):410-8.