Journal
CELLS
Volume 9, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/cells9041019
Keywords
podoplanin (PDPN); near-infrared photoimmunotherapy; malignant pleural mesothelioma
Categories
Funding
- Program for Developing Next-generation Researchers (Japan Science and Technology Agency), KAKEN [18K15923, 17K07299, 19K07705]
- Takeda Science Foundation
- Kowa Life Science Foundation
- Aichi Cancer Research Foundation
- Toyoaki Scholarship Foundation
- Suzuken Memorial Foundation
- Research Grant of the Japan Cancer Society
- Research grant of The Nagoya University Medical Association
- Foundation for Promotion of Cancer Research
- Project Mirai Cancer Research Grant
- Chukyo Choju Research Grant
- Nagoya-Igaku Shinkokai
- AMED [JP19am0401013, JP19am0101078, JP19ae0101028]
- Grants-in-Aid for Scientific Research [19K07705, 18K15923, 17K07299] Funding Source: KAKEN
Ask authors/readers for more resources
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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available