In the first human trial of its kind, a vaccine grown in genetically engineered tobacco plants has proved to be safe, paving the way to one day use it to help combat a potentially fatal form of non-Hodgkin's lymphoma.
Researchers report in the Proceedings of the National Academy of Sciences USA that the experimental vaccine triggered the immune systems of 11 of 16 volunteers (with so-called follicular B-cell lymphoma) to attack their tumors without any apparent dangerous side effects.
Some 18,000 Americans, typically between the ages of 60 and 65, are diagnosed annually with this incurable, slow-growing type of cancer. Study coauthor Ronald Levy, an oncologist at the Stanford University School of Medicine, says that physicians generally take their cues from the disease, waiting to see how fast it is moving—and treating it with toxic chemotherapy (sometimes with radiation) only if it becomes aggressive.
He says that if future trials are successful, the experimental vaccine, which can be made relatively quickly and cheaply, could become a short-term therapy administered immediately after diagnosis to try to keep tumors in check.
"This may not be a replacement for chemotherapies, but a supplement for them," Levy says. "A technology that is fast, like this one, is more amenable to a watchful waiting approach than a technology that is slow to produce."
This and other anti-cancer vaccines work by pumping a patient full of the same protein or antigen that is on the surface of tumor cells. Researchers believe that if the body contains enough of the protein, the immune system will recognize it as a potential danger and send out armies of disease-killing cells to seek and destroy tumors harboring it.
To make the vaccine, researchers took a sample of a patient's tumors, which in this trial were made up of B cells (white blood cells that help the body battle disease and infection). They then extracted the gene from the cells that coded for the antigen they needed (to help the immune system recognize the tumors as threats). The key, researchers say, was to make enough of the protein quickly to prompt an immune response.
In this case, the scientists achieved this by inserting the gene into a plant microbe known a tobacco mosaic virus (TMV). Plants are infected with TMV simply by scratching their leaves and depositing the virus into the tears. Researchers discovered that the virus spreads throughout tobacco plants within a week, in the process cranking out a surfeit of the coveted proteins. The scientists ground the leaves and separated out the antigen, which they then injected into volunteers.
They found that the immune systems of 70 percent of participants perked up when blasted with antigens specific to their cancers. The researchers report mild side effects, such as swelling around the injection site and mild to moderate flu symptoms in some participants within a week of getting the vaccine. Of the original group of 16—who ranged in age from 30 to 64—three died (from the disease, not the vaccine), but 13 are still alive and their diseases are in remission up to eight years since being given the vaccine.
All of the patients also received chemotherapy, so researchers cannot be certain what role, if any, the vaccines played. Levy says more work is being done to assess the vaccine's effectiveness.
Charles Arntzen, a plant biologist at the Arizona State University Biodesign Institute, says a major plus is how fast the vaccine can be whipped up. "I think without the speed," he says, "it would be hard to convince a cancer patient to wait for a vaccine to be developed, rather than going on some other therapy."
Levy is trying to find a new biotech company to begin efficacy trials on humans as soon as possible. He says that a vaccine like this one could be on the market as soon as it proved effective and safe.