A plant virus that infects legumes, the cowpea mosaic virus, has a special ability that you may not have known about: when injected into a tumor, it triggers the immune system to treat the cancereven metastatic cancer.
Researchers at the University of California San Diego and Dartmouth College have studied and tested the cowpea mosaic virus in the form of nanoparticlesas a cancer immunotherapy. Its performance has been unmatched by other cancer-fighting strategies the team has tested. However, the reasons for its failure have remained unclear.
In a new study published in the journalMolecular Pharmaceutics, researchers discover concepts that explain why the cowpea mosaic virus is particularly effective against cancer.
Nicole Steinmetz, a research associate at the University of California of Technology, and Steven Fiering, a professor of microbiology and immunology at Dartmouth. Steinmetz and Fiering have founded a biotechnology company, calledMosaic ImmunoEngineering Inc., which has licensed the cowpea mosaic virus nanotechnology and is working to transform it into a cancer immunotherapy.
According to Steinmetz, the cowpea mosaic plant virus nanoparticle is used as our lead cancer immunotherapy candidate, which is now available for clinical treatment.
Bislang, Steinmetz, Fiering, and their partners had a general idea of how their lead candidate worked. The cowpea mosaic virus nanoparticles, which are infectious in plants but not in mammals, are injected directly inside a tumor to serve as an immune system bait. When the immune cells recognize the virus nanoparticles as foreign agents, they go after the cancerous cells.
Despite Steinmetz''s dedication to taking care of that one tumor, it also establishes a systemic immune response against future metastatic tumors. It has been used in mouse models of melanoma, ovarian cancer, breast cancer, colon cancer, and glioma. It has also improved in the treatment of canine patients with melanoma, breast cancer, and sarcoma.
The cowpea mosaic virus has proven to be effective in triggering an anti-cancer immune response, according to first author Veronique Beiss, a former postdoctoral researcher at Steinmetzs. That''s the answer to the knowledge gap were attempting to fill.
Researchers found that cowpea mosaic virus was compared to two other plant viruses from the same family that have the same shape and size. One virus, the cowpea severe mosaic virus, has a similar RNA sequence and protein composition. The other, the tobacco ring spot virus, is similar only in size. This would be great comparisons to see if this powerful anti-tumor effect may be found in this particular individual strain, according to Steinmetz.
The researchers created plant virus-based nanoparticle immunotherapies and injected them into mice''s melanoma tumors. Each immunotherapy candidate was administered in three doses given 7 days apart. Mice given the cowpea mosaic virus nanoparticles had the highest survival rate 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 examined them. They discovered that the plant viruses all have a protein shell that activates toll-like receptors that are on the surface of immune cells. But this technique, which is particularly true of the cowpea mosaic virus, is that it activates an additional receptor through its RNA. Moreover, triggering an additional receptor, which assists the immune system in determining immunity, making it difficult to look for and ridding tumor
The team''s analysis found that the cowpea mosaic virus enhances the immune response four days after the second dosage. And these levels remained high for a long time. According to Beiss, this long-term immune response is another significant benefit that sets the cowpea mosaic virus apart.
While this opens up about superior potential and effectiveness of cowpea mosaic viruses, Steinmetz admits that there is still plenty of work to be done. Finally, questions have arisen. What happens to this virus nanoparticle in the cell, but not the RNA of other plant viruses? Will understanding the complex journey of this particle through the cell and how it compares to other particles will help us define what makes the cowpea mosaic virus unique against cancer.