Engineers at the University of California, San Diego have uncovered promising evidence that a plant virus could revolutionize cancer immunotherapy. Their research on cowpea mosaic virus (CPMV) nanoparticles, derived from black-eyed pea plants, demonstrates significant anti-tumor effects across multiple cancer types in preclinical studies, with findings published in Cell Biomaterials and Advanced Science.
Unique Immune Activation Mechanism
The cowpea mosaic virus stands apart from other plant viruses in its ability to stimulate robust anti-cancer immune responses. "It is fascinating that CPMV but not other plant viruses stimulates an anti-tumor response," said Nicole Steinmetz, corresponding author and the Leo and Trude Szilard Chancellor's Endowed Chair in the Aiso Yufeng Li Family Department of Chemical and Nano Engineering at UC San Diego's Jacobs School of Engineering.
Research comparing CPMV with the closely related cowpea chlorotic mottle virus (CCMV) revealed critical differences in immune activation. While both viruses are similar in size and cellular uptake, only CPMV induces potent anti-cancer responses. The team discovered that CPMV stimulates type I, II, and III interferons—proteins with established anti-cancer properties—and its RNAs are processed in a way that activates toll-like receptor 7 (TLR7), essential for robust immune responses.
"What we found most exciting is that although human immune cells are not infected by CPMV, they respond to it and are reprogrammed towards an activated state, which ultimately trains them to detect and eradicate cancerous cells," explained Anthony Omole, first author and doctoral student in Steinmetz's lab.
Systemic Treatment Success
The latest research demonstrates that CPMV nanoparticles do not require direct tumor injection to be effective. Systemic administration improved survival rates and inhibited metastasis across various cancer models, including colon, ovarian, melanoma, and breast cancer. When mice were injected with CPMV nanoparticles and challenged with metastatic tumors a week later, they exhibited improved survival rates and reduced tumor growth compared to untreated mice. Remarkably, similar protective effects persisted when mice were challenged with new tumors a month later.
"Here, we do not treat established tumors or metastatic disease—we prevent them from forming. We are providing a systemic treatment to wake up the body's immune system to eliminate the disease before metastases even form and settle," Steinmetz explained.
Post-Surgical Applications
The treatment showed particular promise in post-surgical settings. Administering CPMV nanoparticles after surgical tumor removal resulted in improved survival rates and decreased tumor regrowth in mouse models. "Even if you perform surgery to remove the tumors, no surgery is perfect and there is outgrowth of metastasis if no additional treatment is provided," Steinmetz noted. "Here, we use our plant virus nanoparticles after surgery to boost the immune system to reject any residual disease and prevent circulating tumor cells from metastatic seeding. We found that it works really, really well!"
Manufacturing Advantages
CPMV offers significant advantages as a cost-effective immunotherapy option. Unlike other therapies requiring expensive manufacturing processes, CPMV can be cultivated using molecular farming—grown in plants with sunlight, soil, and water. To produce the nanoparticles, researchers grew black-eyed pea plants in the laboratory and infected them with cowpea mosaic virus. Millions of copies of the virus were grown and harvested in the form of ball-shaped nanoparticles, requiring no further modification before experimental use.
Clinical Translation Plans
The research team is preparing for clinical trials, with plans to conduct safety studies and explore treatment efficacy in pet animals with cancer. "The present study provides important insights into the mechanism of action of CPMV. We are diligently working toward the next steps to ensure that the most potent lead candidate is selected to achieve anti-tumor efficacy and safety," Steinmetz said. "This is the time and we are poised to move this work beyond the bench and toward clinical trials."
Future studies will focus on understanding the mechanisms underlying the immune-boosting properties of cowpea mosaic virus nanoparticles. The research was supported by the National Institutes of Health and the Shaughnessy Family Fund for Nano-ImmunoEngineering at UC San Diego.
