Why this plant virus is so powerful in fighting cancer

For the past seven years, researchers at UC San Diego and Dartmouth College have been studying and testing cowpea mosaic virus (in nanoparticle form) as a cancer immunotherapy, reporting in lab mice and pet dogs promising results
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But the exact reason for its success remains a mystery
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In a new study published in the journal Molecular Pharmacy, researchers uncovered details that explain why cowpea mosaic virus is particularly effective against cancer

The work was led by Nicole Steinmetz, professor of nanoengineering at UC San Diego's Jacobs School of Engineering, and Steven Fiering, professor of microbiology and immunology at Dartmouth's Geisel School of Medicine

"This study helps confirm cowpea mosaic virus nanoparticles as our lead candidate for cancer immunotherapy," Steinmetz said

So far, Steinmetz, Fiering, and their team have a rough idea of ​​how their lead candidate works

The beauty of this approach, Steinmetz

Also interesting, compared to other plant viruses or virus-like particles studied by the researchers, cowpea mosaic virus did the best job of triggering an anticancer immune response

To find out, the researchers compared the cowpea mosaic virus with two other plant viruses from the same family, with the same shape and size

Researchers created plant virus-based nanoparticle immunotherapies and injected them into melanoma tumors in mice

The researchers then extracted immune cells from the spleens and lymph nodes of the treated mice and analyzed them
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They found that these plant viruses have a protein coat that activates toll-like receptors on the surface of immune cells
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But the cowpea mosaic virus is unique in that it activates an additional toll-like receptor through its RNA
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Activating this additional receptor triggers more types of pro-inflammatory proteins that help boost the immune system's anti-cancer response
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In other words, triggering a stronger inflammatory response makes the immune system work harder to find and remove tumors
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The team's analysis also uncovered another unique way in which cowpea mosaic virus enhances the immune response
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Four days after the second injection, the researchers measured high levels of cytokines
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These levels have remained high for an extended period of time
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"We didn't see this in the other two plant viruses
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Cytokine levels peaked very quickly, then dropped, and then disappeared, and this prolonged immune response is another key difference in cowpea mosaic virus
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While this reveals the remarkable potency of cowpea mosaic virus, Steinmetz admits that more work needs to be done
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"The answers we found here lead to even more questions, how is this viral nanoparticle processed in the cell? What happens to its RNA and protein? Why is the Cowpea mosaic virus's RNA recognized, while the The RNA of other plant viruses cannot be identified? Understanding the detailed journey of this particle through the cell, and how it compares to other particles, will help us determine what makes cowpea mosaic virus uniquely effective against cancer
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"

references

Cowpea Mosaic Virus Outperforms Other Members of the Secoviridae as In Situ Vaccine for Cancer Immunotherapy