A familiar example of this is flu shots, which are delivered in your arm but trigger an immune response that protects against a respiratory infection. Fiering started to wonder if a similar approach might be taken with cancer. His idea was that if doctors injected something into a tumor that would cause the body’s immune system to start attacking it, the heightened immune response wouldn’t be limited to just the area around the tumor. The immune system’s T-cells—its frontline soldiers—would also track down any cancer cells that might be lurking elsewhere in the body.
It was an elegant idea, but Fiering had a hard time finding the right stuff to inject into a tumor that would alert the immune system to the attack target. At first, he focused on single-celled parasites and bacteria, but those didn’t elicit the sort of strong immune response that the body would need to take on a tumor. Mammalian viruses didn’t work much better. It was only after attending a talk about plant viruses in medicine by Nicole Steinmetz, a nanoengineer at the University of California, San Diego, that Fiering saw a way forward. Steinmetz and other researchers had shown that plant viruses have useful properties as vaccine-delivery platforms and adjuvants, an ingredient in a vaccine that increases the body’s immune response. It got Fiering thinking: Maybe he could harness this same effect to fight cancer, too.
For more than two decades, Steinmetz has been studying ways to modify plant viruses to do useful things like delivering cancer therapies and vaccines in animals, and treating diseases in plants. “I like to joke that we use dirt and sunlight to produce nanotechnology,” says Steinmetz. “But that’s essentially what we do. We grow plants, infect them, and then harvest the virus. The plant is our bioreactor.”
While he listened to Steinmetz present her work on plant viruses, it dawned on Fiering that those same pathogens might be useful in his work on cancer immunotherapies. After Steinmetz’s talk, he pitched her on a collaboration. It wasn’t something she’d tried before, but she was willing to give it a shot. “We had been developing virus-like particles as cancer therapies and vaccines, so the proposal made sense,” says Steinmetz. “We just never thought about injecting that material directly into the tumor.”
For Steinmetz, the question was which virus to use. There are just over 1,000 known species of plant viruses, but as Fiering and Steinmetz figured out, not all of them are equally good at stimulating the body’s immune system. Because plant viruses aren’t really a threat to humans, the body’s immune system typically doesn’t treat them like one.
In 2015, Steinmetz sent Fiering some cowpea mosaic viruses to test on mice in his lab. It’s one of the best characterized plant viruses; Steinmetz describes it as the “go-to virus” in her medical research. The viral particles are symmetrical, which makes it easy to precisely add molecules to the outside of each one, and they are easy to produce in plants in large quantities.
It seemed like as good a starting point as any, and when the team tested it on tumors in lab mice, it proved to be incredibly effective. As detailed in a paper published later that year in Nature Nanotechnology, the research team discovered that the cowpea mosaic virus was highly effective in treating melanoma, breast, ovarian, and colon tumor models in mice. (Tumor models are growths that are caused by the injection or implantation of cancerous cells into healthy mice.) They found that in all tumor models tested, the plant viral therapy reduced the rate of tumor growth. Depending on the tumor model, growth was slowed by an average of 50 to 100 percent over a two-week period. In some models, it caused the tumor to disappear completely.