Epidermal growth factor receptor-targeted near-infrared photoimmunotherapy for malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a rare, aggressive cancer mostly associated with asbestos exposure. Effective treatments are limited, and the prognosis is extremely poor. Therefore, the development of novel therapeutic approaches is highly desirable. Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that specifically kills target cells. It utilizes an antibody-IRDye700DX conjugate that binds target tumor cells. After near-infrared light irradiation of the tumor, rapid and highly selective cell damage results in immunogenic cell death. Anti-epidermal growth factor receptor (EGFR) antibody-IRDye700DX conjugate has already been approved in Japan for the treatment of head and neck cancer with near-infrared laser light activation. EGFR overexpression in MPM makes it a promising candidate for EGFR-targeted NIR-PIT, but its efficacy has not been reported previously. In this study, we investigated the therapeutic effects of NIR-PIT targeting EGFR using an MPM xenograft mouse model. In vitro, three MPM cell lines (NCI-H28, NCI-H226, and MSTO-211H) showed EGFR overexpression on the cell surface. EGFR-targeted NIR-PIT induced cell death in a dose-dependent manner in all MPM cell lines. In vivo, EGFR expression was verified, and anti-EGFR antibody binding was observed in both NCI-H226 and MSTO-211H tumors. After EGFR-targeted NIR-PIT, histological analysis demonstrated cancer cell death which significantly suppressed tumor growth in both tumor models and significantly extended survival in NCI-H226 tumor-bearing mice. Thus, these results suggest that EGFR-targeted NIR-PIT could be a promising treatment approach for MPM.