Amivantamab restores antitumor immunity in non-small cell lung cancer through EGFR/MET expression-dependent mechanisms
Presenter: Takamasa Ishino, MD;PhD Session: Immune Mechanisms Invoked by Other Therapies and Exposures Time: 4/20/2026 2:00:00 PM → 4/20/2026 5:00:00 PM
Authors
Takamasa Ishino 1 , Ryo Yoshichika 1 , Fumiaki Mukohara 2 , Ken Suzawa 2 , Shinichi Toyooka 3 , Yosuke Togashi 1 1 Department of Tumor Microenvironment, Okayama University, Okayama, Japan, 2 Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University, Okayama, Japan, 3 Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharma, Okayama University, Okayama, Japan
Abstract
Introduction: Epidermal growth factor receptor (EGFR) mutations are one of the most common oncogenic drivers in non–small cell lung cancer (NSCLC). Although EGFR tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated clinical benefits, acquired resistance still limits the long-term efficacy, with activation of MNNG HOS Transforming (MET) signaling serving as a representative bypass mechanism. Recently, amivantamab, a bispecific antibody against EGFR and MET, has shown clinical efficacy. However, its immunological role in human tumors has not been directly investigated. Methods: We analyzed 40 surgically resected fresh NSCLC samples to evaluate EGFR/MET expression and their correlation with immune suppression. Tumor-infiltrating lymphocytes (TILs) were evaluated by flow cytometry and immunohistochemistry. To assess the immunomodulatory effects of amivantamab, tumor digests including viable TILs were cultured ex vivo under conditions with or without amivantamab. Results: EGFR mutations and elevated EGFR protein expression showed a tendency for reduced infiltration of CD8⁺ T cells and dendritic cells (DCs). Ex vivo exposure to amivantamab enhanced CD8⁺ T-cell effector functions and DC maturation in TILs, particularly in tumors with high EGFR/MET expression, independent of EGFR mutation status. Conclusion: This study provides the first direct evidence using fresh human NSCLC samples that amivantamab can restore antitumor immunity through CD8⁺ T-cell activation and DC maturation. Expression levels of EGFR and MET may serve as predictive biomarkers for amivantamab monotherapy as well as for amivantamab-based combination immunotherapies.
Disclosure
T. Ishino, Gilead Sciences, Inc. ). R. Yoshichika, None.. F. Mukohara, None.. K. Suzawa, None. S. Toyooka, TAIHO PHARMA ), Other, Honoraria. Eli Lilly ), Other, Honoraria. Chugai Pharmaceutical ), Other, Honoraria. Astellas Pharma ). GUARDANT Other, Honoraria. AstraZeneca Other, Honoraria. Illumina Other, Honoraria. MERCK Other, Honoraria. CSL Behring Other, Honoraria. Nippon Kayaku Other, Honoraria. Daiichi-Sankyo Other, Honoraria. Ono Pharmaceutical Other, Honoraria. Medtronic Other, Honoraria. Ziosoft Other, Honoraria. NOVARTIS Other, Honoraria. Sysmex and Riken Genesis Other, Honoraria. Y. Togashi, Janssen Pharmaceutical K.K. ). AstraZeneca ), Honoraria. TAIHO PHARMA ). Daiichi-Sankyo ). KOTAI ). KORTUC ). Ono Pharmaceutical Other, Honoraria. Bristol-Myers Squibb Other, Honoraria. Chugai Pharmaceutical Other, Honoraria. Eisai Other, Honoraria. MSD Other, Honoraria.
Cited in
Control: 239 · Presentation Id: 4271 · Meeting 21436