Research Achievements

June 18, 2020 

Shining light on a malignant lung cancer

A near-infrared light treatment could help manage a rare form of lung cancer.

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Treating a rare type of malignant lung cancer could improve, thanks to near-infrared irradiation and a cancer-targeting compound. Nagoya University oncologist Kazuhide Sato and colleagues tested the treatment and published their findings in the journal Cells.

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Malignant pleural mesothelioma (MPM) is a rare type of cancer that affects the lung lining. It rarely spreads to other parts of the body, but is usually diagnosed too late, leading to a poor prognosis and very limited treatment options.

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Sato and colleagues investigated the effectiveness of near-infrared photoimmunotherapy (NIR-PIT) as a treatment strategy for MPM. NIR-PIT has been fast-tracked for approval by the US Food & Drug Administration for treatment of a type of malignant head and neck tumor. For NIR-PIT to work, a cancer-targeting compound must first be injected. The compound is made of an antibody, which targets a specific structure on the cancer cells, and a photoabsorber, called IR700. When near-infrared light is shone on the body part affected by cancer, the compound aggregates on the cancer cell membranes, leading to acute cell rupture and tumor death.

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"The lungs and chest cavity contain a large amount of air and are thus very good at effectively transmitting near-infrared light," says Sato. "NIR-PIT is a safe phototherapy option that can target a region of interest. The antibody-IR700 conjugate is also non-toxic to the body in the absence of near-infrared light irradiation. We thus thought that NIR-PIT could be an effective strategy for controlling localized MPM."

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For NIR-PIT to work on MPM, the scientists needed a compound that specifically targeted MPM cancer cells. They focused their attention on an antibody called NZ-1, which targets a specific part of a transmembrane glycoprotein called podoplanin. Podoplanin is normally found on many cell types in the human body, but is particularly abundant in some types of cancer cells, including MPM.

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The team's research showed that podoplanin was widely expressed in a variety of MPM cell lines. They found that NZ-1 conjugates well with the photoabsorber IR700 and that NZ-1-IR700 specifically bound to podoplanin on cells in the lab. When podoplanin-positive cells, including MPM cancer cells, were mixed with NZ-1-IR700 and then irradiated with near-infrared light, the cells immediately swelled and ruptured.

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The team then injected NZ-1-IR700 in mice with MPM tumors. The compound gradually accumulated at the tumor sites. Shining near-infrared light on the tumor sites led to a reduction of fluorescence from cancer-tagged cells, indicating the treatment worked well as an anti-cancer strategy.

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?The therapy could involve injecting a podoplanin antibody conjugated with a photoabsorber

and then shining near-infrared light into the chest cavity. (Credit: Kazuhide Sato)

?(Click on the image for a larger version.)

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Sato and his colleagues say further studies are needed to find ways that ensure the treatment will not kill healthy podoplanin-positive cells. The researchers also suggest a more focused dose of light could be achieved by shining it into a drainage device inserted into the chest cavity, which is normally used anyway in MPM patients to drain the chest from excess fluids.

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The study, "Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin," was published in the journal Cells on April 20, 2020, at DOI: 10.3390/cells9041019.

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Contact:

Kazuhide Sato

Graduate School of Medicine, Nagoya University

Email: k-sato@med.nagoya-u.ac.jp

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