Using a virus that grows in black-eyed pea plants, nanoengineers at the University of California San Diego developed a replacement treatment that would keep metastatic cancers cornered from the lungs. The treatment not only slowed tumor growth within the lungs of mice with either metastatic carcinoma or melanoma, it also prevented or drastically minimized the spread of those cancers to the lungs of healthy mice that were challenged with the disease.
The research was published Sept. 14 within the journal Advanced Science.
Cancer spread to the lungs is one among the foremost common sorts of metastasis in various cancers. Once there, it’s extremely deadly and difficult to treat.
Researchers at the UC San Diego Jacobs School of Engineering developed an experimental treatment that combats this spread. It involves a bodily injection of a virus called the cowpea mosaic virus. The virus is harmless to animals and humans, but it still registers as a far off invader, thus triggering an immune reaction that would make the body simpler at fighting cancer.
The idea is to use the virus to assist the body’s system recognize and destroy cancer cells within the lungs. The virus itself isn’t infectious in our bodies, but it’s of these danger signals that alarm immune cells to travel into attack mode and look for a pathogen, said Nicole Steinmetz, professor of nanoengineering at UC San Diego and director of the university’s Center for Nano-ImmunoEngineering.
To draw this immune reaction to lung tumors, Steinmetz’s lab engineered nanoparticles made up of the cowpea mosaic virus to focus on a protein within the lungs. The protein, called S100A9, is expressed and secreted by immune cells that help fight infection within the lungs. And there’s one more reason that motivated Steinmetz’s team to focus on this protein: overexpression of S100A9 has been observed to play a task in tumor growth and spread.
“For our immunotherapy to figure within the setting of lung metastasis, we’d like to focus on our nanoparticles to the lung,” said Steinmetz. “Therefore, we created these virus nanoparticles to range in on the lungs by making use of S100A9 because the target protein. Within the lung, the nanoparticles recruit immune cells in order that the tumors don’t take.”
“Because these nanoparticles tend to localize within the lungs, they will change the tumor microenvironment there to become better at fighting off cancer – not just established tumors, but future tumors also ,” said Eric Chung, a bioengineering Ph.D. student in Steinmetz’s lab who is one among the co-first authors on the paper.
To make the nanoparticles, the researchers grew black-eyed pea plants within the lab, infected them with cowpea mosaic virus, and harvested the virus within the sort of ball-shaped nanoparticles. They then attached S100A9-targeting molecules to the surfaces of the particles.
The researchers performed both prevention and treatment studies. within the prevention studies, they first injected the virus nanoparticles into the bloodstreams of healthy mice, then later injected either triple negative carcinoma or melanoma cells in these mice. Treated mice showed a dramatic reduction within the cancers spreading to their lungs compared to untreated mice.
In the treatment studies, the researchers administered the nanoparticles to mice with malignant tumor in their lungs. These mice exhibited smaller lung tumors and survived longer than untreated mice.
What’s remarkable about these results, the researchers means , is that they show efficacy against extremely aggressive neoplastic cell lines. “So any change in survival or lung metastasis is pretty striking,” said Chung. “And the very fact that we get the extent of prevention that we do is basically , really amazing.”
Steinmetz envisions that such a treatment might be especially helpful to patients after they need had a cancerous tumor removed. “It wouldn’t be meant as an injection that’s given to everyone to stop lung tumors. Rather, it might tend to patients who are at high risk of their tumors growing back as a metastatic disease, which frequently manifests within the lung. this is able to offer their lungs protection against cancer metastasis,” she said.
Before the new treatment can reach that stage, the researchers got to do more detailed immunotoxicity and pharmacology studies. Future studies also will explore combining this with other treatments like chemotherapy, checkpoint drugs or radiation.
Chung YH, Park J, Cai H, Steinmetz NF.
S100A9-Targeted Cowpea Mosaic Virus as a Prophylactic and Therapeutic Immunotherapy against Metastatic carcinoma and Melanoma.
Adv Sci (Weinh). 2021 Sep 14:e2101796. doi: 10.1002/advs.202101796
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