In an ironic twist to the relationship between tobacco and human health, it would seem that the future of the plant may lie in growing vaccines against cancer. Researchers in the US took antibodies from patients with a type of lymphoma, grew them in tobacco plants, extracted them, and reinjected the individualized vaccines back into the patients, where in most cases it produced an immune response that helped to fight the cancer.
The research was the work of scientists at the Stanford University School of Medicine in California, and constitutes the first human tests of an injectable vaccine grown in plants. The study was published online ahead of print on 21st July in the Proceedings of the National Academy of Sciences, PNAS.
Scientists have been very interested in using plants instead of animals as a way to produce vaccines because they are potentially cheaper, safer and faster to produce on a large scale. However, plant produced cancer vaccines have not received much research attention, and until this study, there have been no clinical trials in humans.
For the phase 1 trial, Dr Ronald Levy, senior author and professor of oncology and the Robert K. and Helen K. Summy Professor in the School of Medicine, and colleagues, recruited 16 patients who had been newly diagnosed with follicular B cell lymphoma, a type of non-Hodgkin lymphoma that affects the immune system and is diagnosed in about 16,000 people in the US each year.
They isolated single-chain antibodies (scFv) from the tumour of each patient, put them into modified versions of the tobacco mosaic virus, and then infected tobacco plants with the virus by scratching it onto the leaves. The antibody-carrying virus penetrated the cells of the tobacco plants, where it then replicated, along with copies of the antibody.
After a few days, the researchers snipped off the leaves from the tobacco plants, ground them up and purified the antibodies. Just a few plants made enough antibodies for each patient. Patients were then injected with their own individualized vaccine. The trial tested low and high doses, with and without an immune system stimulant called GM-CSF.
Levy and colleagues wrote that:
“Both low and high doses of vaccines, administered alone or co-administered with the adjuvant GM-CSF, were well tolerated with no serious adverse events.”
Over 70 per cent of the patients developed a general immune response (either cellular or humoral) and 47 per cent developed antigen-specific responses and none of the patients experienced any side effects.
The researchers concluded that:
“Collectively, these findings support the conclusion that plant-produced idiotype vaccines are feasible to produce, safe to administer, and a viable option for idiotype-specific immune therapy in follicular lymphoma patients.”
The vaccine works because of a curious habit of follicular B-cell lymphoma, which starts when an immune cell clones itself uncontrollably. But each clone carries the same antibody on its outside surface. This antibody is unique to the lymphoma cell and is not found anywhere else in the body, so it can be used as a target. The vaccine puts more of these antibodies (without the cancer cells) into the patient, giving the immune system a very loud message to attack everything that carries that specific antibody, which of course includes the lymphoma clone cells.
But the procedure only works if the patient is injected with lots of copies of the antibody that is individual to that patient, which means individualized vaccines for each patient.
Follicular B-cell lymphoma is a chronic, incurable disease, that is currently treated with chemotherapy that has such severe side effects that patients often prefer to wait and see how the disease progresses. But vaccines grown in plants, with no side effects, could mean the cancer could be treated earlier and much more aggressively. As Levy explained:
“This would be a way to treat cancer without side effects; the idea is to marshal the body’s own immune system to fight cancer.”
Studies using animals to grow personalized vaccines have had mixed success. A considerable disadvantage of using animals to produce individualized vaccines is the much higher cost (thousands of dollars per patient), much longer time and the added risk that the patient may inherit an animal virus from contaminated cells.
“The plant system has some advantages,” said Levy, adding that it was also “pretty cool technology,” and that is was somewhat “ironic that you would make a treatment for cancer out of tobacco. That appealed to me,” he added, explaining that none of the toxic chemicals found in cigarettes end up in the vaccine.
Another advantage of the plant method, apart from being faster and cheaper, is that the researchers believe antibodies grown this way generate a stronger immune response than animal-grown vaccines. It has something to do with the fact animal and plant cells differ in the way they attach sugars to antibodies during their synthesis; a process called glycosylation that is known to affect antibody activity.
Levy and colleagues are now planning a phase 2 clinical trial to test the plant-based vaccine in a larger group of lymphoma patients.
“Plant-produced idiotype vaccines for the treatment of non-Hodgkin’s lymphoma: Safety and immunogenicity in a phase I clinical study.”
A. A. McCormick, S. Reddy, S. J. Reinl, T. I. Cameron, D. K. Czerwinkski, F. Vojdani, K. M. Hanley, S. J. Garger, E. L. White, J. Novak, J. Barrett, R. B. Holtz, D. Tusé and R. Levy
PNAS published ahead of print July 21, 2008
doi:10.1073/pnas.0803636105
Source: Journal abstract, Stanford Shcool of Medicine news release.
Written by: Catharine Paddock, PhD