Feature: Disease-fighting 'plantibodies'
By Charles Q. Choi
UPI Science News
Published 6/2/2003 5:46 PM
View printer-friendly version
In a greenhouse in Philadelphia sit trays of tobacco plants that one day could help fight rabies. They join plants engineered to fight cancer and other biotech crops designed to generate antibody therapies.
Analysts tell United Press International these plant-made antibodies, or "plantibodies," could prove a real boon to a field expected to yield nearly $13 billion in sales in the next five years.
Antibodies are the high-powered sniping rifles of the body's defense arsenal. The immune system tailor-makes these complex proteins for every intruding microbe, to clamp down on and neutralize enemies.
After decades of effort and hundreds of millions of dollars of expenditures, pharmaceutical companies now have brought about a dozen genetically engineered, "monoclonal-antibody" drugs to market in the United States. Some 300 more are in development, according to biotechnology analyst Alex Hittle at A.G. Edwards in St. Louis. Scientists are even trying to treat patients infected with severe acute respiratory syndrome, better known as SARS, with antibodies -- and with some success.
"They're billion-dollar drugs," biotech analyst Mark Monane of Needham & Co., in New York City, told UPI. Biotech giant Genentech made $1.1 billion alone in 2002 from its antibody drug, Rituxan, for non-Hodgkin's lymphoma, and Amgen projects $1.2 billion to $1.4 billion in sales this year for its arthritis-fighting antibody drug, Enbrel.
"Today, monoclonal antibodies represent the fastest-growing class of therapeutics in the pharmaceutical industry," said Monsanto spokesman Lee Quarles in St. Louis. "Projections indicate that by 2008, there will be more than 70 monoclonal antibodies on the market."
Antibody drugs have proven effective -- but not cheap. At best, they are mass-produced from genetically engineered animal cells fermented in giant vats that require sensitive heat and sterility controls. Antibody therapies against rabies are not mass-produced, but instead are collected from the blood of people or horses who recently were vaccinated against the virus.
At least 10 million people receive anti-rabies antibodies annually. However, horse anti-rabies antibodies can trigger severe, life-threatening allergic reactions, and there is a world shortage of the human anti-rabies medication. Just 10 milliliters of these human proteins can cost $760 to $825. More than 40,000 people die of rabies worldwide every year.
"Traditional fermentation facilities are too expensive and take too long to build to produce the volumes of antibodies necessary for therapies, especially for something like rabies," said Lisa Dry, spokeswoman for the Biotechnology Industry Organization in Washington, D.C.
"It can take $400 million to $500 million to create a traditional vat that uses mammalian cells, and five to seven years to make that," Dry continued. "If you have a product a lot of people want, you almost immediately have this supply-and-demand problem."
She said at one point, there was a waiting list of 12,000 people who wanted Enbrel "because they couldn't make it fast enough. That's why plants are being used as an alternative to mammalian cells to make antibodies."
In findings made public this week in the Proceedings of the National Academy of Sciences, a joint, U.S.-British research team said they have developed a cheap, plant-based way of generating effective anti-rabies antibodies.
Led by plant geneticist Kisung Ko and oral polio vaccine inventor Hilary Koprowski of Thomas Jefferson University in Philadelphia, the team found the antibodies, when given to hamsters infected with rabies, worked just as well as the human ones, but without the nasty side effects.
The researchers have developed a pioneer crop of hundreds of greenhouse-grown tobacco plants implanted with the gene for human anti-rabies antibodies. A 900-acre field of the plants could grow well over a kilogram of the antibodies, enough for roughly 100,000 doses. The researchers plan to boost the productivity of their plants even higher.
"Plants, of course, can be grown everywhere," said researcher Sergei Spitsen, an immunologist at TJU. "Purifying the antibodies is relatively inexpensive (and) we hope to find a way to produce inexpensive antibodies that will be affordable, not only in the United States, but around the world."
The main cost advantage of plant-grown over vat-grown antibodies is "you don't have to invest as much in capital and the high-operating expense of a fermentation tank farm," said Jeffrey Price, chairman of Planet Biotechnology in Hayward, Calif. "Antibodies from plants could cost in the zone of $100 to $200 per gram, while antibodies made in cell cultures are in the $200 to $2,000 per gram range."
Price explained plantibodies expand the opportunity for antibodies as therapeutic agents. "They allow you to consider targeting mass markets at a far more reasonable cost. In general, people haven't wanted to target infectious diseases that aren't life-threatening with antibodies because the cost is too high. People aren't going to pay $5,000 to have their cold cured."
The researchers also are working on anti-cancer plantibodies.
Elliott Fineman, Planet Biotechnology's president and CEO, said among the plantibodies his company is developing are two that can fight dental cavities and the common cold. Both are grown in tobacco.
"We're confident we can get at least a kilogram of purified material per acre," Fineman said.
Still, Hittle told UPI, the success of plantibodies "is by no means an obvious or foregone conclusion."
He said the U.S. Food and Drug Administration no doubt will be very cautious in approving drugs derived from plantibodies.
"Going forward with plant-based antibodies introduces a whole level of risk," Hittle said. "Even if it's substantially cheaper, companies are going to be cautious. If you have a hot antibody drug, the last thing you want is to get hung up" in the approval process because the manufacturing methods are unusual.
"The theoretical advantages are substantial, and people are ridiculously desperate to redeem tobacco in some way for tobacco farmers," Hittle conceded. "But it's going to be a tough sell."
upi.com |
