A plant virus that infects legumes, called the cowpea mosaic virus, has a special annoyance that you may not have known about it: when injected into a tumor, it causes the immune system to treat the cancereven metastatic cancer.
Researchers at the University of California San Diego and Dartmouth College have been working on and testing the cowpea mosaic virus in the form of nanoparticlesas a cancer immunotherapy. It has shown promising results in lab mice and companion dog patients. Its performance has been unmatched by other cancer-fighting strategies they have tested. However, the reasons for its success have remained unknown.
In a new study published in the journalMolecular Pharmaceutics, researchers uncover concepts that explain why the cowpea mosaic virus in particular is extremely effective against cancer.
Nicole Steinmetz, a biology professor at the University of California, and Steven Fiering, a biology professor at the Geisel School of Medicine at Dartmouth, have led the work. Steinmetz and Fiering are co-founders of a biotechnology company, known as "Mosaic ImmunoEngineering Inc.", which has licensed the cowpea mosaic virus nanotechnology and is planning to transform it into a cancer immunotherapy.
According to Steinmetz, the cowpea mosaic plant virus nanoparticle is the first tumor immunotherapy candidate in the United States, and it is now available as a mechanistic explanation for why it is the most powerful candidate, which further de-risks it for clinical translation.
Bislang, Steinmetz, Fiering, and their teams had a general understanding of how their lead candidate performed. The cowpea mosaic virus nanoparticles, which are infectious in plants but not in mammals, are injected directly inside a tumor to serve as immune system bait. The immune cells recognize the virus nanoparticles as foreign agents and they are fired up to attack. When the immune cells see the virus nanoparticles inside a tumor, they go after the cancerous cells.
The beauty of this technique, said Steinmetz, is that it not only treats that one tumor, but also creates a systemic immune response against future metastatic tumors. It has been found in mouse models of melanoma, ovarian cancer, breast cancer, colon cancer, and glioma. It has also been shown to treat canine patients with melanoma, breast cancer, and sarcoma.
Another important thing is that the cowpea mosaic virus has worked the best in triggering an anti-cancer immune response compared to other plant viruses or virus-like particles that researchers have uncovered. Now we have shown that it works, and now we need to demonstrate what makes it so special that it can resurgence the problem. That''s what we had previously considered.
According to Steinmetz, scientists compared cowpea mosaic virus with 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 structure and protein composition. Another, the tobacco ring spot virus, is similar only in structure. We believe these would be great experiments to see if this powerful anti-tumor effect runs in this particular family of plant viruses. We can then dig deeper by comparing to relatives with and without sequence homology.
The researchers performed plant virus-based nanoparticle immunotherapies and transpose them into mice'' melanoma tumors. Each immunotherapy candidate was administered in three doses administered seven days apart. Mice given the cowpea mosaic virus nanoparticles had the highest survival rate and the most minor tumors, with tumor growth essentially stalling four days after the second dose.
The researchers used them to extract immune cells from the spleen and lymph nodes from the treated mice and determined them. They found that the plant viruses all have a protein shell that activates receptors, known as toll-like receptors, which are on the surface of immune cells. But what''s unique about the cowpea mosaic virus is that it activates an additional toll-like receptor through its RNA. This is because, in other words, the immune system is a lot more difficult to look for and get
The teams'' analysis found another powerful technique in which the cowpea mosaic virus boosts the immune response. Four days after the second dosage, the researchers measured high levels of cytokines. This level of cytokine persists for a long time, but this is not the case with other cowpea mosaic virus.
While this article will highlight the potential and effectiveness of cowpea mosaic viruses, Steinmetz says there is still still work to do. What is the RNA of this cowpea mosaic virus, but not the RNA of other plant viruses? Will you know what makes this cowpea mosaic virus unique to cancer?