Plants Induced to Act as Vaccine Factories for Cancer Treatment

Plants could act as safe, speedy factories for growing antibodies for personalized treatment against a common form of cancer, according to findings in the first human tests of an injectable vaccine grown in tobacco plants.

The treatments, which would vaccinate cancer patients against their malignant cells, could lead to earlier personalized therapy to tackle follicular B-cell lymphoma. Physicians regard follicular B-cell lymphoma as a chronic, incurable disease. The traditional treatment, chemotherapy, has such severe side effects that patients frequently opt for watchful waiting in the early stages of illness. However, plant-grown vaccines, which lack side effects, could allow an earlier, more aggressive management of the cancer.

"This would be a way to treat cancer without side effects,” said Ronald Levy, M.D., professor of oncology at the Stanford University School of Medicine (Stanford, CA, USA), who is the study's senior author. "The idea is to marshal the body's own immune system to fight cancer.”

The findings appeared on July 21, 2008, in the advance online issue of the Proceedings of the [U.S.] National Academy of Science (PNAS). The study was a phase I trial that demonstrated that plant-grown cancer vaccines were safe for patients and could be produced quickly and inexpensively. Sixteen newly diagnosed lymphoma patients received the treatment; none experienced any side effects from plant-grown vaccines. Future studies will evaluate the vaccine's effectiveness.

The cancer vaccines rely on a biologic idiosyncrasy of follicular B-cell lymphoma, which is a type of non-Hodgkin's lymphoma. The cancer is triggered when a single immune cell multiplies uncontrollably, producing clones of itself. The clones all carry the same antibody on their exterior, a marker that is unique to the cancer and is not found on any of the body's healthy cells. Dr. Levy's vaccination approach is to inject many copies of the cancer-specific antibody into a newly diagnosed lymphoma patient, stimulating the patient's immune system to seek and destroy malignant cells.

Earlier trials of this type of vaccine, produced in animal cells and tested in mice and humans, have had mixed success, and the vaccines are not yet commercially available. Growing cancer vaccines in plants could help avoid some of the problems of converting the concept into a real treatment, according to Dr. Levy.

Because each individual's cancer antibody is unique, every patient needs a customized vaccine. Growing personalized vaccines in animal cells takes months, costs thousands of dollars per patient, and comes with the hypothetic risk that a patient might inadvertently be infected with an animal virus that contaminated the cells used to grow the vaccine. Personalized vaccines could also be produced with genetically engineered bacteria, but bacteria-grown vaccines are not ideal, either.

"The plant system has some advantages,” said Dr. Levy, who is also a member of the Stanford Cancer Center. The researchers chose tobacco plants that were genetically engineered to reproduce quantities of the vaccine. To make a tobacco plant produce a human antibody, scientists isolate the antibody from the patient's tumor and put the antibody gene into a modified version of the tobacco mosaic virus. They infect a tobacco plant with the gene-carrying virus by scratching the virus on its leaves. The virus takes the gene into the plant's cells, which then churn out lots of antibodies. After a few days, technicians cut off the plant's leaves, grind them, and purify the antibody. Only a few plants are needed to make sufficient vaccine for each patient.

"The new manufacturing system allows very rapid production of a vaccine,” said Charles Arntzen, Ph.D., a professor of plant biology at the Arizona Biodesign Institute at Arizona State University (Tempe, USA), who was not involved in the research. "I think without the speed, it would be hard to convince a cancer patient to wait for a vaccine to be developed, rather than going on some other therapy.”

"It's pretty cool technology,” Dr. Levy said. "And it's really ironic that you would make a treatment for cancer out of tobacco. That appealed to me.” None of the harmful chemicals found in cigarettes end up in the purified vaccines.

Not only is the technology fast, inexpensive, and safe, but Dr. Levy reported that there is reason to expect that the plant-grown antibodies will generate a stronger immune response than those made in animal cells. Both plant and animal cells attach sugars to antibodies and other proteins during biochemical processing, but the plant and animal sugars are different. The difference might trigger a stronger immune reaction to plant-grown antibodies, according to Dr. Levy.

The next research step is a phase-II clinical trial to test the effectiveness of plant-grown vaccines in a larger group of lymphoma patients, according to Dr. Levy. He is optimistic, adding, "We know that if you get the immune system revved up, it can attack and kill cancer.”

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