Tobacco plants enlisted in war on cancer.

In an ironic twist on its infamous role as a cause of deadly tumors, tobacco might soon offer physicians a way to rapidly make vaccines tailored to fight a patient's specific cancer.

This role reversal stems from the ability of a well-studied pathogen, the tobacco mosaic virus, to force an infected plant to mass-produce the proteins of the virus. A biotech firm has exploited this capability by slipping selected genes into the viruses and using them to turn tobacco into a protein factory.

"Literally every cell becomes infected," says Daniel Tuse of Biosource Technologies in Vacaville, Calif. "The yield is phenomenal, and the [time] that it takes from inoculation to harvest is 2 to 3 weeks."

Biosource has used this technique for a decade, generating commercial enzymes as well as proteins for a potential malaria vaccine. Hoping to showcase the technology further, the company recently approached Ronald Levy of the Stanford University School of Medicine, who has studied vaccines for treating non-Hodgkin's lymphoma.

In this cancer, a single antibody-producing B lymphocyte, or B cell, breaks free of normal growth controls and copies itself endlessly. The cancer has a weak spot, however. All the lymphoma cells in a patient sport the same protein, the unique antibody made by the original B cell, on their surface. Researchers have shown that inoculations with this shared protein can stimulate the immune system to attack the lymphoma cells of that patient.

"We have a surface molecule unique to each lymphoma," says Levy. "It's really a problem of how you can make these [vaccines] fast and cheap."

"Our goal is to produce customized vaccines to treat non-Hodgkin's lymphoma in a matter of weeks after receiving the biopsy," adds Tuse.

To test that possibility, Tuse, Levy, and their colleagues used tobacco plants to make a fragment of an antibody from a mouse B cell lymphoma. Although physicians have had promising results with cancer vaccines made of complete antibodies, researchers are just beginning to test antibody fragments in people.

It can take months to a year to genetically engineer plants to make antibodies (SN: 12/5/98, p. 359). In just a month, however, Biosource used an engineered tobacco mosaic virus to make tobacco plants churn out large quantities of the antibody fragment. When this fragment was injected into healthy mice as a cancer vaccine, the animals produced antibodies targeting the protein, the scientists report in Jan. 19 Proceedings of the National Academy of Sciences.

More important, the vaccine protected the mice against injections of the lymphoma cells from which the researchers had isolated the antibody fragment.

Biosource and Levy's group has already infected tobacco plants with antibody-fragment genes from people with non-Hodgkin's lymphoma. Tuse predicts that customized vaccines could help thousands of patients. "We're not there yet. We have to show that these things work in people," he cautions.

If researchers can identify appropriate target molecules on tumors of solid tissues, Biosource also hopes to use their tobacco technology to make patient-specific vaccines for diseases such as breast and prostate cancer.

"The creation of unique vaccines for individuals or groups of individuals is clearly the way people are thinking about treatment for the future," says Charles J. Arntzen of the Boyce Thompson Institute for Plant Research in Ithaca, N.Y.