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Detection of Circulating Tumor Cells (CTCs) in Malignant Pleural Mesothelioma (MPM) with the “Universal” CTC-Chip and An Anti-Podoplanin Antibody NZ-1.2
Open AccessArticle

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

1
Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
2
B3-Unit, Advanced Analytical and Diagnostic Imaging Center (AADIC)/Medical Engineering Unit (MEU), Nagoya University Institute for Advanced Research, Nagoya 466-8550, Japan
3
Nagoya University Institute for Advanced Research, S-YLC, Nagoya 464-8601, Japan
4
Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
5
Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Nagoya 464-8601, Japan
6
Department of Biomolecular Engineering, Nagoya University Graduate School of Engineering, Nagoya 464-8601, Japan
7
Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
8
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1088, USA
9
New Industry Creation Hatchery Center, Tohoku University, Sendai 980-8575, Japan
10
National Hospital Organization, Nagoya Medical Center, Nagoya 460-0001, Japan
*
Author to whom correspondence should be addressed.
These authors equally contributed to this work.
Cells 2020, 9(4), 1019; https://doi.org/10.3390/cells9041019
Received: 23 March 2020 / Revised: 15 April 2020 / Accepted: 16 April 2020 / Published: 20 April 2020
(This article belongs to the Special Issue Structure and Function of Podoplanin (PDPN) in Disease)
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. View Full-Text
Keywords: podoplanin (PDPN); near-infrared photoimmunotherapy; malignant pleural mesothelioma podoplanin (PDPN); near-infrared photoimmunotherapy; malignant pleural mesothelioma
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Nishinaga, Y.; Sato, K.; Yasui, H.; Taki, S.; Takahashi, K.; Shimizu, M.; Endo, R.; Koike, C.; Kuramoto, N.; Nakamura, S.; Fukui, T.; Yukawa, H.; Baba, Y.; K. Kaneko, M.; Chen-Yoshikawa, T.F.; Kobayashi, H.; Kato, Y.; Hasegawa, Y. Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin. Cells 2020, 9, 1019.

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