Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin

• Published in: Cells (Basel, Switzerland) Switzerland), 2020-04, Vol.9 (4), p.1019
• Main Authors: Nishinaga, Yuko, Sato, Kazuhide, Yasui, Hirotoshi, Taki, Shunichi, Takahashi, Kazuomi, Shimizu, Misae, Endo, Rena, Koike, Chiaki, Kuramoto, Noriko, Nakamura, Shota, Fukui, Takayuki, Yukawa, Hiroshi, Baba, Yoshinobu, K Kaneko, Mika, Chen-Yoshikawa, Toyofumi F, Kobayashi, Hisataka, Kato, Yukinari, Hasegawa, Yoshinori
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Antitumor activity; Apoptosis; Cancer; Cell Line, Tumor; Cytotoxicity; Humans; I.R. radiation; Immunoconjugates - pharmacology; Immunoglobulins; Immunotherapy - methods; Laboratory animals; Light therapy; Lung Neoplasms - drug therapy; Lung Neoplasms - immunology; malignant pleural mesothelioma; Medical research; Membrane Glycoproteins - drug effects; Mesothelioma; Mesothelioma, Malignant - drug therapy; Mesothelioma, Malignant - immunology; Mesothelioma, Malignant - pathology; Metastasis; Mice, Nude; Microscopy; Molecular Targeted Therapy; near-infrared photoimmunotherapy; Phototherapy; Phototherapy - methods; podoplanin (PDPN); Spectrum analysis; Tumors; Xenograft Model Antitumor Assays - methods
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9041019

Malignant pleural mesothelioma (MPM) has extremely limited treatment despite a poor prognosis. Moreover, molecular targeted therapy for MPM has not yet been implemented; thus, a new targeted therapy is highly desirable. Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer therapy that combines the specificity of antibodies for targeting tumors with toxicity induced by the photoabsorber after exposure to NIR-light. In this study, we developed a new phototherapy targeting podoplanin (PDPN) for MPM with the use of both NIR-PIT and an anti-PDPN antibody, NZ-1. An antibody-photosensitizer conjugate consisting of NZ-1 and phthalocyanine dye was synthesized. In vitro NIR-PIT-induced cytotoxicity was measured with both dead cell staining and luciferase activity on various MPM cell lines. In vivo NIR-PIT was examined in both the flank tumor and orthotopic mouse model with in vivo real-time imaging. In vitro NIR-PIT-induced cytotoxicity was NIR-light dose dependent. In vivo NIR-PIT led to significant reduction in both tumor volume and luciferase activity in a flank model ( < 0.05, NIR-PIT group versus NZ-1-IR700 group). The PDPN-targeted NIR-PIT resulted in a significant antitumor effect in an MPM orthotopic mouse model ( < 0.05, NIR-PIT group versus NZ-1-IR700 group). This study suggests that PDPN-targeted NIR-PIT could be a new promising treatment for MPM.