Harvesting Monoclonal Antibodies from Plants
When monoclonal antibodies were first developed 20 years ago, they were hyped as a magic bullet for curing cancer and other diseases. However, killing cancer cells with these immune proteins, which are artificially produced and which neutralize one specific antigen or foreign protein, was not as straightforward as first assumed, and clinical failures occurred. Moreover, the high cost of producing monoclonal antibodies by traditional cell fermentation methods limited their applications. These setbacks have forced scientists to look more realistically at monoclonal antibodies.
Now, researchers at EPIcyte Pharmaceutical, based in San Diego, California, hope to revitalize interest in monoclonal antibodies with a new technology that produces large supplies of the proteins inexpensively. Their new technology uses green plants to churn out large quantities of "plantibodies." After undergoing some genetic engineering, plant cells easily assemble monoclonal antibodies. Plants are expected to be able to make unlimited quantities of plantibodies at prices that will be 25-100 times less expensive than cell fermentation methods.
The current standard cell fermentation methods can produce just 5-10 kg of a monoclonal antibody in a year. In comparison, EPIcyte plans to produce 10,000 kg of key plantibodies per year. The current high cost of monoclonal antibodies, which ranges from $200 to $1,000 per gram, is predicted to fall to $10-100 per gram or less as plants produce tons of plantibodies.
A large, cheap supply means that new medical, consumer, and industrial applications for monoclonal antibodies could become economically feasible. For instance, plantibodies could target toxicants or pollutants in large-scale water purification systems, theorizes biochemist Andrew Hiatt, a developer of plantibodies who cofounded EPIcyte in 1996 along with plant physiologist Mich Hein. Plantibodies that sequester heavy metals or radioactive compounds could become tools for bioremediation.
The first plantibodies were produced in tobacco plants, but to meet commercial demands, EPIcyte is developing corn that produces monoclonal antibodies. Corn is the most widely grown crop worldwide, and its seed (kernel) naturally stores plantibodies in a low-moisture environment that is loaded with protective protease inhibitors. Stored plantibodies can be purified as needed by standard milling procedures. The high-molecular-weight 300,000-400,000 daltons) plantibodies easily separate from the low-molecular-weight (< 50,000 daltons) corn proteins when solubilized.
The first clinical evidence of plantibodies' effectiveness appeared at Guy's Hospital in London. A plantibody against Streptococcus mutans, which produces lactic acid and erodes tooth enamel, was produced in tobacco plants. When brushed onto human teeth for three weeks, the plantibody prevented tooth decay for up to four months, as described in the May 1998 issue of Nature Medicine. The plantibody "specifically inhibits Streptococcus from binding to tooth surfaces," says Hiatt.
EPIcyte holds exclusive license for plantibody technology from The Scripps Research Institute in La Jolla, California. In alliance with ReProtect of Baltimore, Maryland, EPIcyte is developing preclinical topical gels that contain plantibodies for herpesvirus types 1 and 2. In a study published in the December 1998 issue of Nature Biotechnology, scientists at ReProtect applied an experimental plantibody to the vaginas of mice, which prevented infection with genital herpes. EPIcyte and ReProtect scientists are planning a joint project to make a more potent herpes plantibody to protect newborn babies against transmission of herpes from infected mothers during delivery.
"The greatest potential for monoclonal antibodies lies in prevention," says Kevin Whaley, a reproductive biologist at The Johns Hopkins University in Baltimore who also works for ReProtect. From a public health perspective, plantibodies are ideally suited for preventing sexually transmitted diseases as over-the-counter products. More than 5 million people in the United States are infected with sexually transmitted diseases annually at an estimated cost of $12 billion in medical treatment. Whaley says, "[Monoclonal] antibodies are so potent and so specific, they can be used in novel ways," such as personal lubricants, gels, or controlled-release devices for vaginal insertion. To accommodate personal preferences, several different user-friendly formulations for plantibodies will be developed, says Whaley. |
