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

Abstract

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 (p < 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 (p < 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.

• Authors: Yuko Nishinaga, Kazuhide Sato, Hirotoshi Yasui, Shunichi Taki, Kazuomi Takahashi, Misae Shimizu, Rena Endo, Chiaki Koike, Noriko Kuramoto, Shota Nakamura, Takayuki Fukui, Hiroshi Yukawa, Yoshinobu Baba, Mika K Kaneko, Toyofumi F Chen-Yoshikawa, Hisataka Kobayashi, Yukinari Kato, Yoshinori Hasegawa
• Journal: Cells (Cells) Vol. 9 Issue 4 (04 20 2020) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 32326079 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gp38 protein, mouse
• Immunoconjugates
• Membrane Glycoproteins
• PDPN protein, human

Topics

• Animals
• Cell Line, Tumor
• Humans
• Immunoconjugates (pharmacology)
• Immunotherapy (methods)
• Lung Neoplasms (drug therapy, immunology)
• Membrane Glycoproteins (drug effects)
• Mesothelioma, Malignant (drug therapy, immunology, pathology)
• Mice, Nude
• Molecular Targeted Therapy
• Phototherapy (methods)
• Xenograft Model Antitumor Assays (methods)