CSU Sacramento Professor on the trail of disease-fighting fruit

Could a tomato, one day, keep cholera away? Or produce therapeutic antibodies to treat cancer?

Scientists at California State University, Sacramento have taken an important step toward developing tomatoes as a possible source of edible vaccines and other proteins such as therapeutic antibodies. Biology professor Nicholas Ewing and graduate student Seungil Ro have identified and recently patented a portion of a gene that could turn tomatoes into low-cost, disease-relieving agents.

Currently, animal cell cultures are used to produce highly effective but expensive vaccines and anti-cancer antibodies, such as Genentech's herceptin antibody. Since this is such a costly method, a number of groups are using plants to produce the antibodies, including Vacaville's Large Scale Biology.

The novelty of Ewing and Ro's approach was the choice of the tomato as a production system.
Their discovery - Promoter of the Tomato Expansion Gene LeEXP-1 - is a genetic "switch" that can be used to trigger the activation of any gene placed adjacent to it. To produce antibodies, the antibody gene is cloned from an animal cell line and placed adjacent to the LeEXP-1 promoter. When this new gene is transferred back into tomato plants, the antibody gene is turned on in tomato fruit, which leads to the accumulation of antibodies. The antibodies can then be purified from the fruit.

For edible vaccines, a different gene - one from the organism being vaccinated against - would be inserted adjacent to the LeEXP-1 promoter and transferred in the tomato. These fruit would then contain the protein of the organism. Consumption of the fruit then could generate an immune response that protects the individual from exposure to the organism itself in the future.
Ewing notes that they still have a way to go toward their long-range goal of a tomato-based vaccine. They are just beginning to test the levels of protein they may be able to produce. But if the work comes to fruition, Ewing foresees a great potential for use, especially in developing countries.

"Regular vaccines are often too expensive - they have to be refrigerated, you have to have clean needles," Ewing says. "While the edible vaccines would still need to be administered by a health professional, they would be much cheaper."

The process could be used for an existing vaccine or as a way to develop vaccines. "I'd like to see it used for vaccines that pharmaceutical companies don't devote much time and money to, such as in developing countries where there's not a lot of money to be made in fighting diseases that impact large numbers of people," Ewing says.

The discovery of the promoter of the LeEXP-1 gene isn't the only reason Ewing is pursing the tomato as his potential source. Previous efforts to produce edible vaccines using potatoes would have required subjects to eat the tubers raw, since cooking would alter the chemistry. Ewing thought it might be better to try something that people will eat uncooked, so he looked at the tomato.

Also for proteins that may later be purified, tomatoes may be superior to sources being used now such as tobacco, corn or soybeans, so they could produce larger amounts for lower costs, he says. There is also less pollen transfer than with other plants and therefore less risk of cross-contamination.

By summer Ewing expects to be able to put some test plants in greenhouses to test how well the system will work. Eventually he hopes to test some in a field near a local biotech facility, buffered from other plants.