Antibody Work on Plants Widens Medical Horizons
Researchers at the Scripps Clinic in La Jolla have developed a new, inexpensive technique for producing specialized antibodies that promises to open up a whole new area of medicine, including cancer therapy, and to greatly expand medical diagnostics.
The technique also could be used to give agricultural crops a functioning “immune system” that would protect them against insects, funguses and other pathogens and to create new plants that could be used to clean up polluted waterways and soil.
“This could spawn a variety of new industries,” Scripps molecular biologist Andrew Hiatt said in a telephone interview.
Antibodies are complex proteins, produced by white blood cells, that target invading microorganisms and foreign chemicals for destruction by the immune system. Their key property is that a given antibody will bind to only one invading chemical or cell without damaging substances that the body needs. This property is known as specificity.
Antibodies for therapeutic and diagnostic purposes are now produced in animal-cell cultures at a cost of thousands of dollars per gram. Hiatt reports in today’s issue of the journal Nature that he has developed a technique for producing the antibodies in plants that would reduce the cost of unpurified antibodies to as little as 10 cents per gram.
One of the first applications of the new technique may be the manufacture of antibodies against lung tumors. Researchers at Scripps are now testing mouse antibodies in humans and, if the tests are successful, the new technique could be used to make much larger quantities of the antibody for future human therapy.
“This could be an extremely important development,” said Gary Wilcox, president of Ingene Inc., a Santa Monica-based company that is itself developing less expensive ways of producing antibodies. “From a global perspective, the more choices we have for producing antibodies, the better off we are.”
The use of antibodies was revolutionized in 1975 by the discovery of techniques for producing large quantities of a single antibody. Georges Kohler and Cesar Milstein of the Laboratory for Molecular Biology in Cambridge, England, isolated single, short-lived white blood cells that produced one antibody and fused them with long-lived cancer cells.
The resulting cells, called hybridomas, inherit immortality--but not the ability to produce disease--from the cancer cells, and the white blood cell’s ability to produce one antibody. Their progeny continue to produce only one antibody, called a monoclonal antibody because it is derived from a single, cloned cell.
Because they will bind to only one substance, monoclonal antibodies are extremely accurate in diagnostics, for measuring minute quantities of such materials as drugs, vitamins, hormones and a broad spectrum of other metabolic products in blood, urine and other solutions. They are commonly used in hospitals, physicians’ offices, and even in home test kits, such as those for pregnancy and colorectal cancer.
But hybridomas currently used to produce monoclonal antibodies can become unstable over time, changing the characteristics of the antibodies. If the plant-derived antibodies are more stable, as Hiatt expects, “that would certainly be a benefit” in the design of test kits, said Sidney Aroesty, president of Diagnostic Products Corp. in Los Angeles.
The new technology could have greater impact on the use of antibodies in medical therapy. Antibodies against tumor cells, for example, will seek such cells out in the body and target them for immune attack. Toxins, anti-cancer drugs and radioactive isotopes can be attached to the antibodies to increase their killing efficiency. Radioactively labeled isotopes can also be used to locate the position of hidden tumors in the body.
Monoclonal antibodies have other medical applications as well. An antibody called OKT-3 is now widely used to prevent rejection in organ transplants by destroying the body’s own antibodies that are attacking the foreign organs. Many researchers think that monoclonal antibodies can also be used to treat autoimmune diseases such as diabetes, multiple sclerosis, and arthritis.
Most such uses are still experimental, and the market is now estimated at only about $3.5 million per year. The trade paper Genetic Engineering News predicts that it will grow to $3.5 billion by 1995.
Cancer therapy with monoclonal antibodies requires about a gram of material per patient per treatment, Hiatt said, making it quite expensive. The discovery announced today could make monoclonal antibody therapy much more widely available by making it much less expensive.
Hiatt and his colleagues at Scripps used standard genetic engineering techniques to insert the gene coding for a particular antibody into tobacco cells, which were then grown into plants. When the plants had fully grown, the antibody accounted for as much as 1.3% of the total protein in its leaves.
The gene for the antibody was passed along to the plants’ progeny, and they produced in the same quantity.
The Scripps researchers then isolated the antibodies and compared them to the same antibody produced by conventional techniques. They were “virtually identical,” Hiatt said. The specific antibody they were using carries out a chemical reaction, but does not have any medical application. Preliminary studies, however, suggest that the technique could be used to make any other antibody desired.
But the new technology could have the greatest impact on agriculture and industry, Ingene’s Wilcox said. Price reductions will convert antibodies into a “commodity,” a chemical produced in large volumes at low costs.
The new technology could push antibodies into applications that are now prohibitively expensive. Such applications could include purification of other biological products, carrying out chemical reactions, and protecting crops against pathogens.
The research at Scripps was sponsored by PPG Industries of Pittsburgh. A spokesman for the company, John Ruch, said Wednesday that the technique was an “extremely important discovery” that will yield “cost-effective production” of monoclonal antibodies. PPG has filed for patents on the process and is “actively investigating a broad range of applications,” he added.
Both Ruch and Hiatt cautioned, however, that a great deal of research must be conducted before there are any commercial applications of the technique.
