Researchers at UC San Diego reveal how the cowpea mosaic virus (CPMV) activates the immune system to fight cancer, offering a promising, cost-effective immunotherapy.
Engineers at the University of California, San Diego are shining a light on a plant virus that shows substantial promise as a potent immunotherapy for cancer. The team has uncovered valuable insights into how the cowpea mosaic virus (CPMV) activates the body’s immune system to target and destroy cancer cells — a breakthrough discovery published in the journal Cell Biomaterials.
Typically found in black-eyed peas, CPMV is emerging as a low-cost, highly effective cancer treatment. Unlike other plant viruses, CPMV uniquely stimulates an immune response that not only targets the primary tumor but also establishes long-lasting memory to combat metastatic tumors elsewhere.
“It is fascinating that CPMV but not other plant viruses stimulates an anti-tumor response,” corresponding author Nicole Steinmetz, 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, said in a news release.
In preclinical trials involving mouse models and canine cancer patients, CPMV has shown remarkable anti-tumor effects. When injected into tumors, CPMV recruits innate immune cells like neutrophils, macrophages and natural killer cells to the tumor site. Simultaneously, it activates B cells and T cells, creating a systemic and long-lasting anti-tumor response.
“This work gives us insight into how CPMV works so well,” added first author Anthony Omole, a chemical and nano engineering doctoral student in Steinmetz’s lab. “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.”
To understand why CPMV outperforms other plant viruses, the team compared it with the cowpea chlorotic mottle virus (CCMV), a closely related virus lacking anti-tumor capabilities. Both viruses are similar in size and uptake by human immune cells, but only CPMV induces a potent anti-cancer response.
The researchers discovered that CPMV stimulates type I, II and III interferons — proteins with known anti-cancer properties. These interferons play a critical role in the immune system’s ability to identify and destroy cancer cells. Moreover, CPMV RNAs are processed in a way that activates toll-like receptor 7 (TLR7), essential for a robust immune response, unlike the RNAs from CCMV.
CPMV also offers a significant advantage 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.
“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 added. “This is the time and we are poised to move this work beyond the bench and toward clinical trials.”