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Tobacco-derived 'plantibodies' enter the fight against Ebola


By Sharon Begley

(Reuters) - Drugmakers' use of the tobacco plant as a fast and cheap way to produce novel biotechnology treatments is gaining global attention because of its role in an experimental Ebola therapy.

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."

What Is ZMapp? Could It Be A Cure For Ebola?
"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.

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.

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cmr256 August 06 2014 at 1:35 PM

Yes, use the drug in Africa - those poor patients are almost for sure going to
die; and there is no harm using this
new drug to possibly save lives - why not? Tobacco takes lives by lung cancer and now it is Tobacco's turn
to give back life. There is a good and bad side to almost everything.

Flag Reply +27 rate up
7 replies
clarewrite August 06 2014 at 1:41 PM

Tobacco has several medicinal qualities - as do most plants from which drugs are derived. When I was a kid on the farm in KY (where we grew tobacco) we would tie a tobacco leaf around the leg of a horse or a cow if they got a cut, and the cut would heal faster - also would numb the pain. Nothing it all bad - nothing is all good.

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4 replies
johnolexa August 06 2014 at 2:34 PM

I understand, but still hate the testing on lab animals, just a little research shows a horrible life they lead until they are of no use any longer. Wish, as smart as they are, they could come up with a better way to test. I know they will one day.

Flag Reply +14 rate up
4 replies
Randy August 06 2014 at 2:41 PM

Oh the horror.... after decades of the ultra far left and the nanny culture attempting to destroy tobacco farmers and now tobacco may be the magic bullet to stop ebola....just what are flaming liberals, buttinskis and self appointed know it all going to do now?

Flag Reply +10 rate up
5 replies
debnaert August 06 2014 at 2:55 PM

That OLD enemy Tobacco might JUST save your worthless rear end! But, it's OK to SMOKE marijuana.... HYPOCRITES!

Flag Reply +9 rate up
dwtomczyk August 06 2014 at 2:20 PM

let me see the options. there are two.
1) die or 2) try the vaccine or die.

Flag Reply +5 rate up
1 reply
briabran dwtomczyk August 06 2014 at 10:13 PM

No, some people have built antibodies against Ebola, although rare, and survived. The doctor that was helping in Liberia and contracted the disease also received antibodies from a 14 year old boy that survived the virus.

Flag Reply 0 rate up
baldbiker2 August 06 2014 at 2:59 PM

Darn, you mean you liberals couldnt find a cure for ebola from pot? Wow, the liberal sphincters are blowing as I type.

Flag Reply +5 rate up
2 replies
jep121212 baldbiker2 August 06 2014 at 7:20 PM

Do you have more guns than teeth? Just asking?

Flag Reply +3 rate up
1 reply
cdub340 jep121212 August 06 2014 at 7:32 PM

WELL SAID!!!

Flag +2 rate up
brenhatestwinkie baldbiker2 August 06 2014 at 8:59 PM

bagger hot air is no cure

Flag Reply +1 rate up
user34603 August 06 2014 at 2:01 PM

What is 'controversial' about a tobacco plant used to make a drug component? If they made the component from gunpowder, would that be 'controversial, as well ? Hell, no. Typical liberal bias to attack by inference against tobacco no matter the value. You'd think it was researchers smoking Camels unfiltered to produce the component to fight Ebola.

Flag Reply +5 rate up
4 replies
Mike August 06 2014 at 1:43 PM

Ebola cigarettes coming soon.

Flag Reply +5 rate up
4 replies
hawtree August 06 2014 at 1:36 PM

Now if we could only find a use for that scourge of a plant Kudzu!

Flag Reply +5 rate up
3 replies
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