Robatumumab Overview

Introduction of Robatumumab

Robatumumab, also known as SCH 717454 and MK-7454, is a monoclonal antibody developed by Merck and Schering-Plough and act as an antineoplastic agent. It binds to the insulin-like growth factor 1 receptor (IGF-1R) with very high affinity. This antibody inhibits proliferation of a number of cell lines in soft agar as well as in vivo in the human ovarian tumor xenograft model. These observations were extended to pediatric cancers including osteosarcoma and Ewing sarcoma in preclinical experiments. About this time, it was shown that improved lymphocyte recovery following chemotherapy was associated with improved prognosis in patients with Ewing sarcoma; similar observations also have been made for osteosarcoma patients. Thus, better immune function may affect survival in both Ewing sarcoma and osteosarcoma. But, phase 2 clinical trials in patients with colorectal cancer, osteosarcoma and Ewing's sarcoma are terminated by Merck.

Mechanism of Action of Robatumumab

The insulin family of growth factors is an evolutionally conserved system which plays a crucial role in the growth and development of many tissues and the regulation of overall growth and metabolism. This system comprises three receptors [insulin receptor (IR), IGF-1 receptor (IGF-1R), and IGF-2/mannose 6-phosphate receptor (M-6-PR)], three ligands (insulin, IGF-1, and IGF-2), and six known types of circulating IGF-binding proteins (IGFBP1-6). The IGF-1R is highly homologous to the IR.

The IGF-1R is a receptor tyrosine kinase with a structure of a heterotetrameric glycoprotein composed of two α and two β subunits, post-transcriptionally linked by disulfide bonds, which regulates cell survival and cell cycle progression via the PI3K/Akt and extracellular signal regulated kinase pathways through insulin receptor substrate-1to-4 (IRS-1to-4) and Src-homology collagen (Shc) adapter proteins. Phosphorylation of the IRS adapter molecules on one hand triggers activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, whereas, on the other hand, the Shc adapter activates signaling by the Ras/Raf/MEK/Erk signaling pathway. IGF-IR seems to be expressed in most human cancers. The two IGF-1R ligands, IGF-1 and IGF-2, have been implicated in cancer initiation and progression.

In the past decades, a large amount of evidence has emphasized that IGF-IR play a key role in the transformation of cells, cancer cell proliferation, as well as in metastatic events, associated in various types of human cancers. It seems that inhibition of IGF-IR signaling can generate antineoplastic effects. A number of monoclonal antibodies have been developed to target the receptor itself, which bind to the extracellular domains of the IGF-1R and block ligand binding. A feature common to all anti-IGF-1R antibodies, probably more important than the blocking activity itself, is their ability to down-regulate of the IGF-1R overtime by promoting internalization of the receptor. Receptor targeting antibodies might have important therapeutic advantages, concerning both specificity and toxicity. A variety of fully human anti-IGF-1R monoclonal antibodies have been characterized and showed strong anti-tumor activity in vitro and in vivo.

Robatumumab is a fully human antibody directed inhibit binding of IGF-1 and IGF-2 to IGF-1R, block the activation of IGF-1R homodimers and IGF-1R/IR hybrid receptors, but not IR homodimers, and promote down-regulation of IGF-1R, which is implicated in the growth and metastatic phenotype of a broad range of malignancies.

Figure 1 Mechanism of Action of Robatumumab

Clinical Projects of Robatumumab *

What We Provide

Therapeutic Antibody

Robatumumab

We provide high-quality Robatumumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term=Robatumumab&cntry=&state=&city=&dist=

For research use only. Not intended for any clinical use.