A plant virus that infects legumes, referred to as the cowpea mosaic virus, has a special power that you may not have known about: when it is injected into a tumor, it is responsible for the immune system to treat the cancereven metastatic cancer.
Researchers at the University of California San Diego and Dartmouth College have been doing research and testing cowpea mosaic virusin the form of nanoparticlesas a cancer immunotherapy. It has found promising results in lab mice and companion dog patients. Its performance has been unmatched by other cancer-fighting strategies they have developed. However, the exact reasons for its success have remained a mystery.
In a new study published in the journalMolecular Pharmaceutics, the researchers uncover information that explain why the cowpea mosaic virus, particularly, is extremely effective against cancer.
Nicole Steinmetz, a biology professor at the University of California, and Steven Fiering, a microbiology and immunology professor at Dartmouth. Steinmetz and Fiering are the co-founders of 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 the most powerful candidate for clinical translation because of his mechanistic results.
Bisher, Steinmetz, Fiering, and their partners had a common idea of how their lead candidate was. 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. When the immune cells recognize the virus nanoparticles, they go after the cancerous cells.
The challenge of this approach, noted Steinmetz, is that it not only takes care of that one tumor, but it also establishes a systemic immune response against any metastatic and future tumors. It''s commonly seen in mouse models of melanoma, ovarian cancer, breast cancer, colon cancer, and glioma. It''s also achieved success in treating canine patients with melanoma, breast cancer, and sarcoma.
A cowpea mosaic virus has performed the best in triggering an anti-cancer immune response than other plant viruses or virus-like particles studied. Now we have demonstrated that it works, and it is now crucial that it can make a difference in this kind of response, according to first author Veronique Beiss, a former postdoctoral researcher. Thats the gap in knowledge was attempting to fill.
The researchers used cowpea mosaic virus to compare 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, according to Steinmetz. We can also look deeper by comparing to relatives with and without sequence homology.
Several experiments were performed in three doses, each with cowpea mosaic virus nanoparticles, which had the highest survival rate and the smallest tumors, and tumor growth stalled four days after the second dosage.
Researchers extracted immune cells from the spleen and lymph nodes from the treated mice and analysed them. They found that the plant viruses all have a protein shell that activates receptors called toll-like receptors, which are on the surface of immune cells. However, this mechanism, called cytokines, is unique to the cowpea mosaic virus, which helps maintain the immune system''s anti-cancer response. In other words, triggering a stronger inflammatory response makes the immune system difficult to look for and
The teams study found another particular technique in which the cowpea mosaic virus boosts immune responses. Four days after the second dose, the researchers measured high levels of cytokines. This situation is not the same as the previous two plant viruses. According to Beiss, this prolonged immune response is also important.
While this paper reveals how cowpea mosaic viruses excel in potency and efficacy, Steinmetz said there is still more work to be done. These are the first steps we have learned here. What happens to this viral nanoparticle, but not the RNA of other plant viruses? We will also learn about how this particle flows through the cell and how it compares to other particles. This article will help us determine what makes this cowpea mosaic virus uniquely effective against cancer.