Photoimmunotherapy for Mesothelioma Reduces Tumor Volume in Mice

Japanese researchers testing photoimmunotherapy for mesothelioma say they used the technology to successfully reduce the size of tumors in mice.

Scientists at the National Cancer Institute in the US developed near-infrared photoimmunotherapy (NIR-PIT). It is a new type of cancer immunotherapy that uses a chemical to make some cells more sensitive to light. When light is directed at these cells, they die.

In their new study of photoimmunotherapy for mesothelioma, the Japanese team targeted podoplanin. Podoplanin is a glycoprotein. Many mesothelioma tumors overexpress podoplanin. 

Targeting Mesothelioma Tumors with Light

Malignant mesothelioma is a fast-growing membrane cancer caused by asbestos exposure. Standard cancer therapies do not work well for mesothelioma. Cancer researchers around the world are looking for alternative treatments. 

Immunotherapy is one of the most promising new approaches for asbestos cancer. Immunotherapy harnesses the immune system to help fight cancer. Photoimmunotherapy for mesothelioma takes the idea a step further by incorporating light into the mix. 

The effectiveness of photoimmunotherapy depends on finding the best way to sensitize the target cells. One way researchers have used photoimmunotherapy for mesothelioma is to destroy the cells that help mesothelioma tumors ‘hide’ from the immune system. 

Another possibility is to sensitize cancer cells themselves. This can be done by targeting a protein they produce. These cancer cells can then be destroyed with light. 

A New Test of Photoimmunotherapy for Mesothelioma

In the new Japanese study of photoimmunotherapy for mesothelioma, scientists targeted podoplanin (PDPN). Pleural mesothelioma cells produce more PDPN than healthy cells. 

The team made a new drug by mixing an anti-podoplanin antibody called NZ-1 with a photosensitizer. Cultured cancer cells treated with the drug died when exposed to light. The more light, the more deadly the effect. 

Then researchers gave the photoimmunotherapy drug to mice with implanted mesothelioma tumors. For tumors in their flanks, the treatment “led to a significant reduction” in tumor volume. 

The next step was to test the treatment on mesothelioma tumors in the normal location. This is called an orthotopic tumor. In people, pleural mesothelioma grows on the membrane around the lungs. 

“The PDPN-targeted NIR-PIT resulted in a significant antitumor effect in an MPM orthotopic mouse model,” writes lead author Yuko Nishinaga with Nagoya University. “This study suggests that PDPN-targeted NIR-PIT could be a new promising treatment for malignant pleural mesothelioma.”

Another possible use of photoimmunotherapy for mesothelioma is to kill cancer cells left behind after mesothelioma surgery. 

Sources:

Nishinaga, Y, et al, “Targeted Phototherapy for Malignant Pleural Mesothelioma: Near-Infrared Photoimmunotherapy Targeting Podoplanin”, April 20, 2020, Cells, Epub ahead of print, https://www.mdpi.com/2073-4409/9/4/1019