Using a virus grown in black-eyed pea plants, nano engineers at the University of California San Diego have developed a new treatment that can keep metastatic cancer away from the lungs.
Treatment not only slows the growth of tumors in the lungs of mice with metastatic breast cancer or melanoma, it prevents or drastically reduces the spread of this cancer to the lungs of healthy rats who have been challenged with the disease.
The research was published in September. 14 in the Journal of Advanced Science.
Lung cancer is one of the most common forms of metastasis to various cancers. Once there, it is extremely fatal and difficult to treat.
Researchers at the UC San Diego Jacobs School of Engineering have developed an experimental treatment that fights this spread. It involves a physical injection of a plant virus called a cowpea mosaic virus. The virus is harmful to animals and humans, but it is still noted as a foreign invader, thus stimulating the immune response which can make the body more effective in fighting cancer.
Plant viruses are used by the body’s immune system to identify and destroy cancer cells in the lungs. “The virus itself is not contagious in our bodies, but it has all these danger signs that immune cells go into attack mode and detect pathogens,” said Nicole Steinmetz, professor of nanotechnology at UC San Diego and director of the university’s Center for Director. Nano-immuno engineering.
To trigger this immune response in lung tumors, Steinmetz’s lab engineered nanoparticles made of Cowpia mosaic virus to target proteins in the lungs. The protein, called S100A9, is expressed and secreted by immune cells that help fight infections in the lungs. And there is another reason that led Steinmetz’s team to target this protein: Excessive expression of S100A9 has been found to play a role in tumor growth and spread.
“In order for our immunotherapy to work in the configuration of lung metastases, we need to target our nanoparticles in the lungs,” Steinmetz said. “So, we made this plant virus nanoparticles at home in the lungs using S100A9 as the target protein. In the lungs, nanoparticles recruit immune cells to prevent tumors. ”
“Because these nanoparticles localize in the lungs, they can alter the tumor’s microscopic environment to become more adept at fighting cancer – not just established tumors, but future tumors as well,” said Eric Chung, PhD in bioengineering. A student in Steinmetz’s lab who is one of the first co-authors of the paper.
To make nanoparticles, the researchers grew black-eyed pea plants in the lab, infected them with the cowpea mosaic virus, and harvested the virus in the form of ball-shaped nanoparticles. They then attached S100A9-target molecules to the particle surface.
Researchers studied both prevention and treatment. In preventive studies, they first injected plant virus nanoparticles into the bloodstream of healthy rats, and then later injected triple-negative breast cancer or melanoma cells into these rats. Untreated rats showed a dramatic reduction in the spread of cancer in their lungs compared to untreated rats.
In the treatment study, the researchers administered nanoparticles to rats with metastatic tumors in their lungs. These rats exhibited small lung tumors and survived longer than untreated rats.
What is remarkable about these results, the researchers point out, is that they show efficacy against highly invasive cancer cell lines. “So any change in survival or lung metastasis is very exciting,” Chung said. “And the fact that the level of prevention we get is really, really amazing.”
Stanmetz envisioned that such treatment could be especially helpful to patients after the cancerous tumor has been removed. “It simply came to our notice then. Instead, it will be given to patients who are at increased risk of developing their tumors as metastatic disease, which often manifests in the lungs. This will protect their lungs from cancer metastasis, ”she said.
Before new treatments reach that stage, researchers need to study immunotoxicity and pharmacology in more detail. Future studies will combine this with other treatments such as chemotherapy, checkpoint medications or radiation.
Paper: “S100A 9-targeted cowpea mosaic virus as prophylactic and therapeutic immunotherapy against metastatic breast cancer and melanoma.” In addition to Young Hun (Eric) Chung, co-authors of the study include Juan Park and Hui Kaino. Nicole Steinmetz serves as the corresponding author of this work.