Amatuximab Overview

Introduction of Amatuximab

Amatuximab, alternative names: MORAb-009, anti-MSLN monoclonal antibody (MAb) is a chimeric, humanized IgG1/k MAb that targets the cell surface Mesothelin (MSLN). The precursor of MORAb-009 was isolated by Chowdhury et al in 1998 56 from a mouse splenic mRNA and was then optimized by fusing the gene encoding MSLN Fv (SS1 scFv) with human IgG1 and kappa regions. It was first designed to treat patients with mesothelin-positive cancers (pancreatic, ovarian, mesothelioma and lung). Amatuximab is not yet commercially available, and the highest development phase is Phase II. In addition, on 16 January 2014, orphan designation (EU/3/13/1222) was granted by the European Commission to Eisai Europe Limited, United Kingdom, for amatuximab for the treatment of malignant mesothelioma.

Mechanism of Action of Amatuximab

Mesothelin (MSLN) is a glycoprotein, detectable on the surface of mesothelial cells and is a glycosyl-phosphatidyl inositol (GPI)-linked membrane protein of 40 kDa over-expressed in all pancreatic adenocarcinoma and mesothelioma, in >70% of ovarian adenocarcinoma, and in non-small cell lung and colorectal cancers. Expression in normal tissues is limited to mesothelial cells lining the pleura, pericardium and peritoneum. Although its biological function in normal cells is completely clarified, it is overexpressed in many types of cancer, and in cancerous cells, it may be involved in the promotion of cell proliferation, adhesion and migration, chemotherapy resistance, and inhibition of apoptosis. The cancer antigen 125 (CA125) tumor-shed antigen (TSA) has immunosuppressive activities via binding to regulatory Siglec-type receptors, and most recently, through the direct binding to a subset of IgG1 isotype monoclonal antibodies (mAbs). Mesothelin binds to CA125, a specific epitope expressed on MUC16, a transmembrane mucin. The interaction between CA125, which is present on a majority of mesothelioma cells, and mesothelin has been suggested to facilitate implantation and metastasis of mesothelioma. This mechanism along with the tumor's ability to manipulate naturally occurring immune checkpoint pathways provide complementary ways by which tumors avert host immune responses. Amatuximab, a chimeric anti-mesothelin monoclonal antibody, elicits antibody-dependent cellular cytotoxicity against mesothelin-expressing tumor cells and inhibits heterotypic adhesion of mesothelin-positive tumor cells to CA125-expressing tumor cells. The substance can potentially reduce tumor growth by inhibiting MSLN binding to the extracellular substrate and also by antibody-dependent cellular cytotoxicity (ADCC).

Fig 1. Mechanism of Action of Amatuximab

Table 1. Clinical Projects of Amatuximab*

What We Provide

Therapeutic Antibody

Amatuximab

We provide high-quality Amatuximab 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.

Reference
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?term=Amatuximab

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