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 The treatment, which had been tested only in lab animals before
being given to two American medical workers in Liberia, consists of
proteins called monoclonal antibodies that bind to and inactivate
the Ebola virus.
For decades biotech companies have produced such antibodies by
growing genetically engineered mouse cells in enormous metal
bioreactors. But in the case of the new Ebola treatment ZMapp,
developed by Mapp Pharmaceuticals, the antibodies were produced in
tobacco plants at Kentucky Bioprocessing, a unit of tobacco giant
Reynolds American.
The tobacco-plant-produced monoclonals have been dubbed "plantibodies."
"Tobacco makes for a good vehicle to express the antibodies because
it is inexpensive and it can produce a lot," said Erica Ollmann
Saphire, a professor at The Scripps Research Institute and a
prominent researcher in viral hemorrhagic fever diseases like Ebola.
"It is grown in a greenhouse and you can manufacture kilograms of
the materials. It is much less expensive than cell culture."
In the standard method of genetic engineering, DNA is slipped into
bacteria, and the microbes produce a protein that can be used to
combat a disease.
A competing approach called molecular "pharming" uses a plant
instead of bacteria. In the case of the Ebola treatment, Mapp uses
the common tobacco plant, Nicotiana benthanmianas.
The process is very similar. A gene is inserted into a virus that is
then used to infect the tobacco plant. The virus acts like a
micro-Trojan Horse, ferrying the engineered DNA into the plant.
Cells infected with the virus and the gene it is carrying produce
the target protein. The tobacco leaves are then harvested and
processed to extract the protein, which is purified.
ZMapp's protein is a monoclonal antibody, which resembles ordinary
disease-fighting antibodies but has a highly specific affinity for
particular cells, including viruses such as Ebola. It attaches
itself to the virus cells and inactivates them.
APPROVAL PROCESS
The drug so far has only been produced in very small quantities, but
interest in it is stoking debate over whether it should be made more
widely available to the hundreds of people stricken with Ebola in
Africa while it remains untested.
“We want to have a huge impact on the Ebola outbreak,” Mapp CEO
Kevin Whaley said in an interview at company headquarters in San
Diego. "We would love to play a bigger role.”
Whaley said he was not aware of any significant safety issues with
the serum. He would not discuss whether the company has been
contacted about providing the drug overseas.
But he did note the novel manufacturing process carries its own
risk, and would have to be cleared by the U.S. Food and Drug
Administration as part of the approval process.
The FDA would, for example, have to be satisfied that the plant
extraction process had not led to contamination of the resulting
drug.
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The tobacco plant grows quickly, said Reynolds spokesman David
Howard, and "it takes only about a week (after the genes are
introduced) before you can begin extracting the protein."
He declined to say how much medication each plant can yield or
whether Kentucky Bioprocessing is in a position to produce ZMapp in
significant quantities.
Scripps' Saphire said it can still take anywhere from one to three
months to produce the ZMapp serum for wider use given the
complexities of the process.
PENTAGON FUNDING
In 2007, Kentucky Bioprocessing entered into an agreement with Mapp
Biopharmaceutical and the Biodesign Institute of Arizona State
University to refine the tobacco-plant approach. The approach
attracted funding support from the Pentagon's Defense Advanced
Research Projects Agency (DARPA).
For all the hope, however, the plant technique has delivered few
commercial products. In 2012 the FDA okayed a drug for the rare
genetic disorder Gaucher disease from Israel's Protalix
BioTherapeutics and Pfizer. Called Elelyso, it is made in carrot
cells, and is the only such drug to reach the market.
Other companies have fallen far short, though it is not clear if the
technique was to blame. Calgary-based SemBioSys Genetics Inc, which
used safflowers to produce an experimental diabetes drug, folded in
2012 before it finished clinical trials.
Even Kentucky Bioprocessing, which at one point was developing
monoclonal antibodies against HIV (the virus that causes AIDS), C.
difficile bacterial infection, and the human papillomavirus, has
dropped the last two projects, Howard said.
Last year Mitsubishi Tanabe Pharma Corp acquired a majority share of
Quebec City-based Medicago, which is developing influenza and other
vaccines using the tobacco-plant technology. The other 40 percent is
owned by tobacco giant Philip Morris International.
(Reporting by Sharon Begley, Toni Clarke and Deena Beasley; Editing
by Michele Gershberg and Martin Howell)
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