Turning plants into antibody factories.

Turning plants into antibody factories

Disease-fighting or pollution-reducing antibodies could become a large-scale agricultural crop, suggest molecular biologists who have genetically engineered tobacco plants to produce large amounts of specifically designed antibody molecules. Like the antibodies of an animal's immune system, the plant-made antibodies, which the scientists call "plantibodies," strongly and selectively bind to only one or a few types of molecules. Normally, plants do not manufacture antibodies and instead deploy other kinds of defensive molecules to disarm biologically threatening chemicals, bacteria or viruses.

To get plants to make antibodies, Andrew Hiatt, Robert Cafferkey and Katherine Bowdish of the Research Institute of Scripps Clinic in La Jolla, Calif., use a series of steps to shuttle two mouse genes, which together code for an antibody molecule, into the nuclei of two different tobacco plant cells. Once in their respective cells, the foreign genes become inserted into the cells' own genetic code. The two genes are derived from a modified line of mouse immune-system cells that other Scripps researchers had developed to produce unusual, catalytic antibodies that not only bind to specific chemical targets called carboxylic esters, but also chemically slice them in two (SN: 9/2/89, p.152).

The scientists use the genetically altered cells to grow entire tobacco plants, some of which produce one or the other of the two antibody parts. After crossing two plants, each of which makes one antibody part, researchers find a certain proportion of the progeny plants produce fully assembled antibodies. "Preliminary results show that catalytic activity is maintained [in plantibodies]," Hiatt told SCIENCE NEWS.

"It's a new technology that's going to be applicable to some pretty important problems such as environmental pollution and possibly cancer therapy," Hiatt says. "I also think there is the possibility of introducing into plants an almost unlimited amount of [disease] resistance" for protecting the food supply, he added. With an admittedly optimistic and rough calculation, Hiatt predicts that a pound of plant-made antibodies could sell for under $100, compared with the $2 million-plus price tag for an equivalent load of identical antibodies made using existing monoclonal antibody technology.

By growing crops of antibody-producing plants, scientists for the first time would have access to industrial quantities of antibody molecules. In one type of large-scale application, plants containing, say, dioxin-binding antibodies might serve as biofilters that could draw in dioxin and clean contaminated soils. To further the cancer-fighting prospects of plantibodies, the researchers now are working with a Scripps immunologist in an attempt to put genes for human-tumor-attacking antibodies into plant cells.

Scientists must overcome severe challenges before plantibodies become mainstream. For one, antibody-making tobacco plants contain lots of naturally toxic chemicals that would have to be removed before their antibody cargo could be used for medical purposes. "No one has developed the capability of purifying kilogram quantities of antibody," Hiatt says. To make purification easier, the researchers are trying to transform less toxic plant cells, such as alfalfa or soybeans, into antibody-makers. Another potential problem lies in the possibility that plantibodies will elicit autoimmune or other health-threatening responses in people.

Molecular biologist Hermann Oppermann of Creative Biomolecules, a biotechnology company in Hopkinton, Mass., says the Scripps approach to producing proteins such as antibodies is slower than bacteria-based processes, though he agrees that plants might prove better suited for the large-scale applications Hiatt envisions.