Plant viruses have special power in fighting cancer, study says

Its performance was unmatched by other anti-cancer strategies the team tested. But the exact reason for its success remains a mystery.

In a new study published in the journal Molecular MedicineResearchers have uncovered details that explain why cowpox mosaic virus in particular is particularly effective in fighting cancer.

A biotech startup, called Mosaic ImmunoEngineering Inc., has licensed cowpea mosaic virus nanotechnology and is working on moving it into the clinic as cancer immunotherapy.

This study helps confirm cowpea mosaic virus nanoparticles as our leading cancer immunotherapy candidate.“Steinmetz, who is also the director of the Center for NanoImmunoEngineering at UC San Diego, said.

Now that we have the mechanistic data to explain why it is the most likely candidate, this further reduces the risk for clinical outbreaks.. “

So far, Steinmetz, Fiering, and their teams have had a general idea of ​​how their main candidate should work. The cowpox mosaic virus nanoparticles, which infect plants but not mammals, are injected directly into the tumor to prey on the immune system.

The body’s immune cells recognize the virus’s nanoparticles as foreign and begin to attack. When immune cells see the virus’ nanoparticles inside the tumor, they hunt down the cancer cells.

Not only does it take care of that one tumor, but it also kicks off a systemic immune response against any and future metastatic tumors.

Researchers have seen it work in mouse models of melanoma, ovarian cancer, breast cancer, colon cancer, and glioma. They have also had success using it to treat canine patients with melanoma, breast cancer, and sarcoma.

What’s also interesting is that cowpox mosaic virus works best in triggering an antitumor immune response compared to other plant viruses or virus seeds that the researchers studied.

First author Veronique Beiss, a postdoctoral researcher in Steinmetz’s lab, said:. “

To find out, the researchers compared cowpox mosaic virus with two other plant viruses of the same family that are similar in shape and size. One virus, cowpox severe mosaic virus, shares a similar RNA sequence and protein composition.

The other, the tobacco ring spot virus, is similar only in structure. “We think these will be great comparisons to see if this powerful anti-tumor effect runs in this particular family of plant viruses.“Said Steinmetz.”And we can dig deeper by comparing with relatives with and without sequence homology. “

The researchers created nanoparticle immunotherapy based on plant viruses and injected them into the melanoma tumors of mice. Each immunotherapy candidate was given three doses 7 days apart. Mice given cowpox mosaic virus nanoparticles had the highest survival rates and the smallest tumors, with tumor growth essentially stalling four days after the second dose.

The researchers then extracted immune cells from the spleen and lymph nodes from the treated mice and analyzed them. They found that all plant viruses have a protein coat that activates receptors, called toll-like receptors, located on the surface of immune cells.

The cowpox mosaic virus activates an additional phone-like receptor through its RNA. Activation of this additional receptor activates a variety of anti-inflammatory proteins called cytokines, which enhance the immune system’s anti-cancer response.


The team’s analysis also found another unique way that cowpox mosaic virus enhances the immune response. Four days after the second dose, the researchers measured high levels of cytokines. And these levels remain high for a long time.

We don’t see this with the other two plant viruses. Cytokine levels peak rapidly, then drop and disappear“Beiss said.”This sustained immune response is another key differentiator that sets cowpox mosaic virus apart. “

While this sheds light on the superior ability and effectiveness of the cowpox mosaic virus, Steinmetz acknowledges that more work remains to be done. “The answers we’ve discovered here have opened up more questions,” she speaks.

How is this viral nanoparticle handled in the cell? What happens to RNA and its proteins? Why is it possible to recognize the RNA of cowpox mosaic virus but not the RNA of other plant viruses? Understanding this particle’s detailed journey through the cell and how it compares to other particles will help us determine what makes cowpox mosaic virus unique against cancer.. “

Source: Medindia

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