Edible plant viruses teach the immune system to kill cancer

The virus that once infected with black-eyed peas is now a competitor against cancer.

Researchers at the University of California, San Diego discovered how the Cow Bean Moses virus (CPMV) reprogrammed human immune cells to attack tumors-never infected them. Unlike other plant viruses, CPMV triggers an effective immune response, absorbs white blood cells and activates long-term anti-tumor memory. New research published in Cellular biological materialssheds light on why CPMV stands out and can accelerate human clinical trials as low-cost, plant growth immunotherapy.

How plant viruses become immune coaches

CPMV is not a virus that infects people. In fact, it doesn’t even target mammalian cells. However, when scientists inject it directly into the tumor, something striking happens: immune cells flood the site, treating the tumor as a threat and starting to clear it. Even more impressive is that this reaction usually runs across the body, attacking distant untreated tumors in waves of whole body defense.

“What we found most exciting was that although human immune cells were not infected with CPMV, they responded to it and reprogrammed the activated state,” said Anthony Omole, first author of Chemistry and Nanoengineering. “This ultimately trains them to detect and eliminate cancer cells.”

What makes CPMV so different from other plant viruses?

To answer this question, the UC San Diego team compared CPMV to its nearly cousin’s cousin’s green spotted virus (CCMV), which has similar size and shape but has no anti-cancer effects. Both viruses enter human immune cells at similar rates. But the similarities stopped.

• CPMV activates type I, II and III interferons – powered immune proteins with known anticancer effects
• In contrast, CCMV stimulates interleukins to produce inflammation rather than tumor clearance
• The RNA of CPMV lasts longer inside the cell and reaches the inner solution, activates Toll-like receptor 7 (TLR7) in this somatic body, a key trigger for antiviral and antitumor immunity
• CPMV appears to be entering through specific receptors such as SR-A1, which further affects how it is processed

“This work gives us a deep understanding of how CPMV works well,” Omore said. The virus is essentially a “foreign invader” and the immune system recognizes the harmful ways we usually associate with the virus.

Training the immune system for long-term memory

In detailed experiments using human blood cells, CPMV stimulated the production of interferons and chemokines such as IP-10, which recruited cancer-killing CD8+ T cells. Single-cell RNA sequencing shows that CPMV exposure moves immune cell behavior at the genetic level, especially between monocytes and dendritic cells. The virus even alters the expression of long-term non-coding RNA, suggesting that deeper epigenetic rewiring may lead to trained immunity.

Unlike conventional cancer therapies that directly target tumor cells, CPMV appears to guide the immune system smarter and faster. This effect is sufficient to prevent tumor growth in some animal models, suggesting durable protection even after several weeks of exposure.

Made from plants and powered by sunlight

Another major advantage of CPMV is how to make it. The virus can be grown in black-eyed pea plants using standard agricultural methods. This means that sunlight, soil and water (not bioreactors or gene editing) can produce effective cancer agents.

“It can grow in plants using sunlight, soil and water,” Omore stressed, in stark contrast to the complex and expensive manufacturing required by many immunotherapy and biomedicines.

Going to the clinic

Although the study focuses on laboratory and preclinical models, researchers are working to push CPMV to clinical trials. The critical next step involves ensuring that the most effective and safest version of the virus is selected for human testing.

“This study provides important insights into the mechanism of action of CPMV,” said Nicole Steinmetz, donation chair of the University of California, San Diego. “We are working hard toward the next step to ensure the most effective primary candidates are selected for anti-tumor efficacy and safety.”

With its unique immune effects and affordable production, CPMV can represent a new field of cancer immunotherapy – one not in the laboratory, but in modest legume leaves.

Journals and Funds

Posted in: Cellular biological materialsVolume 1, Issue 6

doi: 10.1016/j.cellbio.2025.06.005

funds: National Institutes of Health (R01 CA224605, R01 CA253615, R01 CA274640), American Cancer Society, FM Kirby Foundation, Mission Boost Foundation, Mission Boost Grant, Sloan Foundation, Sloan Foundation, etc.

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