JMT101 plus osimertinib led to a thorough and sustained EGFR blockade
To probe the mechanism of action behind the combination treatment, we first evaluated their impacts on EGFR signaling in 20ins cell lines. Immunoblot analysis was performed on Ba/F3 cells expressing EGFR insASV, insSVD and insNPH. Combining JMT101 with afatinib or osimertinib strongly inhibited EGFR signaling activation in three cell lines (Supplementary Fig We noticed that the addition of JMT101 reduced total EGFR levels in three cell lines. To visualize these impacts, we performed immunofluorescence staining on Ba/F3 cells expressing EGFR insASV under specific treatments. Compared with cells treated with afatinib or osimertinib alone, cells receiving the combination therapy exhibited a marked downregulation of total EGFR levels and a trend of EGFR internalization (Supplementary Fig 