Harnessing radiation to improve immunotherapy response in metastatic melanoma

Andrew Z. Wang, MD, a UNC Lineberger member and associate professor in the UNC School of Medicine Department of Radiation Oncology, received an award from the U.S. Army Medical Research Acquisition Activity to study a potential mechanism for improving immunotherapy for metastatic melanoma in the lungs.

Harnessing radiation to improve immunotherapy response in metastatic melanoma click to enlarge Andrew Z. Wang, MD, is a UNC Lineberger member and associate professor in the UNC School of Medicine Department of Radiation Oncology.

A University of North Carolina Lineberger Comprehensive Cancer Center researcher was awarded a two-year, $605,018 contract to develop a novel strategy to improve immunotherapy treatments for melanoma that has spread to the lungs. 

Andrew Z. Wang, MD, a UNC Lineberger member and associate professor in the UNC School of Medicine Department of Radiation Oncology, received the award from the U.S. Army Medical Research Acquisition Activity.

Wang will use the funding to develop a strategy to improve responses to immunotherapy. Specifically, his team plans to tissue engineer cancer metastasis in a dish, treat the cancer cells with lethal radiation, and inject them back to boost immune response. They aim to produce the “abscopal effect,” which can occur with immunotherapy and radiotherapy. And by engineering the tumor microenvironment to be pro-inflammatory, they hypothesize that the response rates would be much higher.

“The idea is that if I can engineer metastasis that looks like a real metastasis, irradiate it, and give it back to the person, we can improve responses to immunotherapy while limiting toxicity,” Wang said.

For the study, they plan to create “decellularized” tissue to engineer melanoma metastasis. In these decellularized models, the cells are stripped away, but important organ microenvironment and biochemical signals remain intact.

“We have engineered cancer metastases that reflect the specific characteristics of what melanoma looks like when it’s spread to the lung,” Wang said. “The model will reflect the behavior of the cancer, and its response to the treatment.”  The models will also be developed to have a pro-inflammatory environment around the tumor to help promote the immune response. 

The U.S. Army Medical Research Acquisition Activity is the awarding and administering acquisition office for this funding award. The work will be supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Peer Reviewed Cancer Research Program, under Award No. W81XWH-16-1-0530. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. In conducting research using animals, the investigator(s) adheres to the laws of the United States and regulations of the Department of Agriculture.