Analysis Affinity of RON Receptor Tyrosine Kinase by KinExA (CAT#: STEM-MB-0026-CJ)

Introduction

The RON receptor tyrosine kinase (MST1R) is expressed at high levels at the surface of many tumor cells of epithelial origin. Overexpressed RON is an oncogenic driver and small molecule inhibitors of the RON kinase and antibodies to the extracellular domain of RON have shown anti-tumor activity in a variety of pre-clinical models. RON is a member of the MET receptor family and its sole ligand is the macrophage stimulating protein (MSP). RON is expressed on myeloid cells and recent studies have shown that the anti-tumor activity of anti-CTLA4 antibodies is enhanced in RON kinase domain knockout mice, suggesting that the inhibition of RON may enhance the activity of anti-CTLA4 treatment in enhancing host anti-tumor immunity. Narnatumab, a humanized monoclonal against RON entered phase I clinical trials but failed for the lack of efficacy, in part because the antibody could not be given at high doses due to solubility issues. The change of form of the antigen resulted in antibodies that exclusively recognized denaturation sensitive epitopes. Some of the new antibodies show remarkable affinity for RON, determined using a kinetic exclusion assay, and bind tightly to the surface expressed form of the protein.