Utilizing a virus that grows in black-eyed pea plants, nanoengineers at the University of California San Diego developed a unusual treatment that could retain metastatic cancers at bay from the lungs.
The treatment not only slowed tumor development in the lungs of mice with either metastatic breast cancer or melanoma, it also averted or drastically minimized the spread of these cancers to the lungs of healthy mice that have been challenged with the disease.
The research was printed Sept. 14 in the journal Advanced Science.
Cancer spread to the lungs is regarded as one of the most general varieties of metastasis in various cancers. Once there, it is far incredibly deadly and complicated to treat.
Researchers at the UC San Diego Jacobs College of Engineering developed an experimental treatment that combats this spread. It entails a bodily injection of a plant virus called the cowpea mosaic virus. The virus is harmless to animals and humans, but it detached registers as a overseas invader, thus triggering an immune response that could make the body extra practical at combating cancer.
The idea is to use the plant virus to help the body’s immune machine acknowledge and extinguish cancer cells in the lungs. The virus itself will not be infectious in our bodies, but it has all these danger signals that alarm immune cells to enter attack mode and search for a pathogen, said Nicole Steinmetz, professor of nanoengineering at UC San Diego and director of the college’s Heart for Nano-ImmunoEngineering.
To draw this immune response to lung tumors, Steinmetz’s lab engineered nanoparticles made from the cowpea mosaic virus to target a protein in the lungs. The protein, called S100A9, is expressed and secreted by immune cells that help fight an infection in the lungs. And there is another reason that motivated Steinmetz’s team to target this protein: overexpression of S100A9 has been observed to play a role in tumor development and spread.
“For our immunotherapy to work in the environment of lung metastasis, we have 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.”
“Because these nanoparticles are inclined to localize in the lungs, they can change the tumor microenvironment there to develop into extra adept at combating off cancer — not suitable established tumors, but future tumors as well,” said Eric Chung, a bioengineering Ph.D. scholar in Steinmetz’s lab who is regarded as one of the co-first authors on the paper.
To make the nanoparticles, the researchers grew black-eyed pea plants in the lab, infected them with cowpea mosaic virus, and harvested the virus in the make of ball-shaped nanoparticles. They then attached S100A9-targeting molecules to the surfaces of the particles.
The researchers carried out both prevention and treatment research. In the prevention research, they first injected the plant virus nanoparticles into the bloodstreams of healthy mice, and then later injected either triple negative breast cancer or melanoma cells in these mice. Treated mice confirmed a dramatic reduction in the cancers spreading to their lungs compared to untreated mice.
In the treatment research, the researchers administered the nanoparticles to mice with metastatic tumor in their lungs. These mice exhibited smaller lung tumors and survived longer than untreated mice.
What’s remarkable about these results, the researchers point out, is that they uncover efficacy against extremely aggressive cancer cell lines. “So any change in survival or lung metastasis is fairly striking,” said Chung. “And the fact that we gain the level of prevention that we achieve is really, really amazing.”
Steinmetz envisions that such a treatment could be especially helpful to patients after they have had a cancerous tumor eliminated. “It wouldn’t be meant as an injection that’s given to each person to forestall lung tumors. Rather, it could be given to patients who are at excessive threat of their tumors growing back as a metastatic disease, which normally manifests in the lung. This is able to offer their lungs safety against cancer metastasis,” she said.
Earlier than the unusual treatment can reach that stage, the researchers deserve to achieve extra detailed immunotoxicity and pharmacology research. Future research will also explore combining this with other treatments such as chemotherapy, checkpoint medication or radiation.
Paper: “S100A9-Targeted Cowpea Mosaic Virus as a Prophylactic and Therapeutic Immunotherapy Against Metastatic Breast Cancer and Melanoma.” In addition to Younger Hun (Eric) Chung, co-first authors of the gape embrace Jooneon Park and Hui Cai. Nicole Steinmetz serves as the corresponding author of this work.
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