Evaluating the therapeutic potential for cancer treatment and revealing the mechanism of telisotuzumab by atomic force microscopy

Telisotuzumab is a monoclonal antibody and a novel anti-cancer drug that specifically binds to the hepatocyte growth factor receptor (HGFR). In this study, we utilized atomic force microscopy (AFM) to examine the mechanical properties of telisotuzumab-treated cancer cells and the biomechanical interplay between telisotuzumab and HGFR. Our observations showed that the binding force of telisotuzumab and hepatocyte growth factor (HGF) with HGFR was nearly identical; however, compared to HGF, telisotuzumab exhibited greater stability and ease of binding. Additionally, telisotuzumab treatment increased the stiffness of A549 lung cancer cells, thus limiting their migration and proliferation. Furthermore, telisotuzumab had a shorter interaction duration, faster bond- formation rate, smaller dissociation rate constant, and required higher activation-free energy for dissociation, which may explain its dominance in the competitive sites. Our study provides valuable insights into the molecular mechanisms underlying the efficacy of telisotuzumab and demonstrates its potential application in further anti-cancer drug design.