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

Our plain-English summary of Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin, by Y. Nishinaga, K. Sato, H. Yasui, et al (Cells, 2020).

The study

• Authors: Y. Nishinaga, K. Sato, H. Yasui, S. Taki, K. Takahashi, M. Shimizu, R. Endo, C. Koike, N. Kuramoto, S. Nakamura, T. Fukui, H. Yukawa, Y. Baba, M. K Kaneko, T.F. Chen-Yoshikawa, H. Kobayashi, Y. Kato, Y. Hasegawa
• Journal: Cells
• Published: 2020;9(4)
• Cited by: 52 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This laboratory and mouse study tested an experimental light-activated treatment, near-infrared photoimmunotherapy, for malignant pleural mesothelioma. The authors attached a light-sensitive dye (IR700) to NZ-1, an antibody that binds a protein called podoplanin. In tumor tissue removed at surgery from 18 patients at Nagoya University Hospital, podoplanin was found in 15 of 18 (83.3%): 13 of 15 epithelioid and 2 of 3 biphasic tumors. Most mesothelioma cell lines carried podoplanin, except Y-MESO-12 and MSTO-211H. In dishes, cell death rose with the light dose. Light alone or the antibody-dye alone caused no significant cell damage. In mice with tumors under the skin (4 per group), treated tumors were significantly smaller than tumors given the antibody-dye without light (p less than 0.05). In mice with tumor cells placed in the chest cavity (at least 3 per group), treated tumors gave significantly less tumor signal than controls (p less than 0.05). The authors concluded the approach could be a promising new treatment. They noted that the antibody also binds normal lymphatic cells and that lighting the chest from outside is difficult.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Preclinical laboratory study: cell-culture experiments and mouse experiments, plus staining of human surgical tumor samples
• Who was studied: Surgical tumor specimens from 18 patients with malignant pleural mesothelioma (15 epithelioid, 3 biphasic; sarcomatoid excluded) operated on at Nagoya University Hospital, Japan, April 2004 to December 2015. Also human mesothelioma cell lines and 8-to-12-week-old female athymic nude mice
• Exposure: No asbestos exposure was studied. The exposure was the experimental treatment: the anti-podoplanin antibody NZ-1 joined to the dye IR700 (NZ-1-IR700), followed by near-infrared light. In the chest-cavity mouse model, mice received 100 µg of NZ-1-IR700 on day 4 and light at 30 J/cm2 on day 5
• Main results:
  • In human surgical specimens, podoplanin staining was positive in 86.7% (13/15) of epithelioid and 66.7% (2/3) of biphasic mesotheliomas
  • Overall, 83.3% (15/18) of the surgical specimens were podoplanin positive
  • Almost all mesothelioma cell lines tested expressed podoplanin, except Y-MESO-12 and MSTO-211H
  • In cell culture, the percentage of cell death after treatment increased as the light dose increased, across the cell lines tested
  • In cell culture, no significant cell damage was seen with light alone or with NZ-1-IR700 alone
  • When podoplanin-positive H2373 cells and podoplanin-negative MSTO-211H cells were grown together and treated, the H2373 cells ruptured and the MSTO-211H cells did not change
  • In mice with tumors under the skin (4 mice per group), treatment significantly reduced tumor volume and luciferase signal compared with controls given NZ-1-IR700 without light (p less than 0.05)
  • In the chest-cavity (pleural disseminated) mouse model with H2373-luc tumors (at least 3 mice per group), treatment led to significant reductions in luciferase activity compared with controls (p less than 0.05). The tumor signal did not increase in treated mice and rose gradually in control mice
• The authors' conclusion: The authors concluded that near-infrared photoimmunotherapy targeting podoplanin with NZ-1 showed sufficient antitumor effects, was feasible, and could be a promising new treatment for malignant pleural mesothelioma
• Limitations the authors state:
  • Podoplanin is also found on normal lymphatic endothelial cells, so the antibody also binds to them
  • It is difficult to light the chest cavity using light sources outside the body
  • In some cases the treatment has limited therapeutic effects

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Podoplanin (D2-40), Prognosis, Targeted Therapy.

Related studies

• Near-infrared photoimmunotherapy targeting GPR87: Development of a humanised anti-GPR87 mAb and therapeutic efficacy on a lung cancer mouse model — H. Yasui, Y. Nishinaga, et al. (2021)
• Anetumab ravtansine: a novel mesothelin-targeting antibody-drug conjugate cures tumors with heterogeneous target expression favored by bystander effect — S. Golfier, C. Kopitz, et al. (2014)
• Therapeutic efficacy evaluation of radioimmunotherapy with 90 Y-labeled anti-podoplanin antibody NZ-12 for mesothelioma — H. Sudo, A.B. Tsuji, et al. (2019)
• Antitumor effect of novel anti-podoplanin antibody NZ-12 against malignant pleural mesothelioma in an orthotopic xenograft model — S. Abe, M.K. Kaneko, et al. (2016)
• Antitumor activity of chLpMab-2, a human-mouse chimeric cancer-specific antihuman podoplanin antibody, via antibody-dependent cellular cytotoxicity — M.K. Kaneko, S. Yamada, et al. (2017)
• Cancer-Specific Antihuman Podoplanin Antibody chLpMab-2f Exerts Antitumor Effects Against Pleural Mesothelioma — A. Yoshida, S. Abe, et al. (2026)

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