Plant virus nanoparticles home in on the lungs to help prevent the spread of cancer.
Image credit: Rodion Kutsaev on Unsplash
Treating metastatic cancer — cancer that spreads from its original site to another part of the body — is one of the most challenging areas of oncology. Survival rate generally depends on the type of cancer, and numerous other factors such as age and overall health, but treatments are limited and may be ineffective due to drug resistance, adverse effects, and dose-limiting toxicity.
Researchers at the University of California San Diego have developed a new immunotherapy that could help keep metastatic cancers from spreading to the lungs. To do this, they used a plant virus that normally infects black-eyed peas to generate an immune response so that the body can recognize and destroy cancer cells making their way into the lungs.
As with other vaccine platforms that use a viral vector, “the virus itself is not infectious in our bodies, but it has all these danger signals that alarm immune cells to go into attack mode and search for a pathogen,” said Nicole Steinmetz, professor of nanoengineering at UC San Diego and director of the university’s Center for Nano-ImmunoEngineering.
Steinmetz and her team targeted a protein called S100A9, which is over-expressed in many different types of cancer including breast, ovarian, skin, bladder, and pancreatic, among many others. This makes it a potentially useful and ubiquitous target for therapeutics, wrote the authors.
“For our immunotherapy to work in the setting of lung metastasis, we need to target our nanoparticles to the lung,” said Steinmetz. “Therefore, we created these plant virus nanoparticles to home in on the lungs by making use of S100A9 as the target protein. Within the lung, the nanoparticles recruit immune cells so that the tumors don’t take.”
To make their immunotherapy, the team grew black-eyed peas in the lab and infected them with the cowpea mosaic virus, after which they harvested as viral nanoparticles that they then attached S100A9-targeting molecules to.
“Because these nanoparticles tend to localize in the lungs, they can change the tumor microenvironment there to become more adept at fighting off cancer — not just established tumors, but future tumors as well,” said Eric Chung, a bioengineering Ph.D. student in Steinmetz’s lab who is one of the co-first authors on the paper.
In mouse models, the immunotherapy was shown to be effective in both treating existing tumors as well as preventing the spread of breast cancer and melanoma. Treated mice showed a dramatic reduction in the cancer’s spread compared to untreated mice, and those that had tumors before injection exhibited smaller lung tumors and survived longer, even against aggressive cancer strains.
“Any change in survival or lung metastasis is pretty striking,” said Chung. “And the fact that we get the level of prevention that we do is really, really amazing.”
“It wouldn’t be meant as an injection that’s given to everyone to prevent lung tumors,” said Steinmetz. “Rather, it would be given to patients who are at high risk of their tumors growing back as a metastatic disease, which often manifests in the lung. This would offer their lungs protection against cancer metastasis.”
More research is needed before this therapy can make it to clinical trials, but the team is hopeful and plans to study combining this with other treatments such as chemotherapy, checkpoint drugs or radiation.
Reference: Young Hun Chung, et al., S100A9-Targeted Cowpea Mosaic Virus as a Prophylactic and Therapeutic Immunotherapy against Metastatic Breast Cancer and Melanoma, Advanced Science (2021). DOI: 10.1002/advs.202101796; quotes adapted from press release provided by the University of California San Diego