🫁 Can amivantamab create a new tumor-directed strategy in diffuse pleural mesothelioma? A new preclinical study examined amivantamab, a bispecific antibody targeting both EGFR and MET, in diffuse pleural mesothelioma. The rationale is clear: transcriptomic, single-cell, and immunohistochemical analyses showed frequent co-expression of EGFR and MET, predominantly in malignant mesothelioma cells. The study found that amivantamab: ➡️ Bound preferentially to mesothelioma cells ➡️ Promoted EGFR and MET receptor internalization ➡️ Blocked ligand-induced signaling through both pathways ➡️ Triggered dose-dependent tumor-cell killing in the presence of PBMCs and NK cells ➡️ Reduced tumor growth in multiple mesothelioma patient-derived xenograft models when combined with human NK cells The proposed mechanism extends beyond receptor blockade. Amivantamab appears to engage natural killer cells and induce antibody-dependent cellular cytotoxicity (ADCC), adding an innate immune component to dual EGFR/MET targeting. In one PDX model, the combination achieved 89.1% tumor growth inhibition. This remains preclinical research, and amivantamab is not yet an established treatment for mesothelioma. Still, the findings support clinical evaluation of bispecific EGFR/MET targeting, particularly in a disease with limited tumor-directed treatment options. Reference: Suzuki et al. Journal of Thoracic Oncology, 2026. @kaushalpar @LYang_Or @AMansfieldMD