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TITLE:  Tobacco as Cancer Research Tool
        Plants Aid in Development of a Vaccine to Fight Tumors
SOURCE: The Washington Post, USA, by Justin Gillis
        http://www.washingtonpost.com/wp-dyn/articles/A4395-2002Jul14.html
DATE:   July 15, 2002

------------------ archive: http://www.gene.ch/genet.html ------------------


Tobacco as Cancer Research Tool
Plants Aid in Development of a Vaccine to Fight Tumors

OWENSBORO, Ky. -- The plants stretching their leaves toward the hot 
Kentucky sun in a greenhouse near here look like any other ordinary tobacco 
plant. They are anything but. Deep inside their cells, they are furiously 
cranking out microscopic fragments of human tumor.

The plants are destined not for a pack of Marlboros, but for a laboratory 
hard by the Owensboro airport. There, the tiny tumor fragments will be 
recovered and processed into vaccines designed to treat a type of cancer 
called lymphoma.

It's a dry run at the moment, but by this fall, vaccines produced this way 
are to be flown to medical suites across the country and injected into 
patients, in one of the largest tests to date of whether vaccination can 
arrest the growth of human tumors.

The shots the patients get will not be of a single, standardized vaccine, 
but rather of a customized product created specifically for each person's 
cancer.

The Kentucky project is sponsored by the California company Large Scale 
Biology Corp., and it chose tobacco -- actually, a close Australian 
relative of American field tobacco -- not for the satisfaction of using 
that maligned plant to treat cancer, but simply because tobacco may be the 
cheapest, fastest vehicle for growing the necessary fragments of tumor.

The project is designed as a test of whether the long-heralded, much-
delayed era of "personalized medicine" is finally at hand -- and whether a 
long history of commercial failure can be overcome to deliver such 
customized treatments at a tolerable price.

"It may be too early to say we're at the dawn" of the age of personalized 
medicine, said Robert L. Erwin, chairman and chief executive of Large Scale 
Biology. "We may be at that very subtle point right before the dawn, where 
you know it's about to happen, but nobody else does."

His company is by no means the only one trying to use tobacco, or other 
plants, to grow drugs. Projects to grow drugs in bulk that way are 
progressing around the country, drawing excitement and a measure of 
environmental concern.

Nor is Large Scale Biology the only company pursuing personalized medical 
treatments -- dozens are. Another company and a National Cancer Institute 
laboratory are well ahead of Large Scale Biology in bringing the idea to 
lymphoma treatment.

But the Kentucky operation is perhaps the most ambitious attempt in the 
country to marry the two approaches -- to use potentially cheap production 
techniques based on plants to create pharmaceuticals customized for 
individual patients.

Bringing a single new drug to market usually takes 10 years, if all goes 
well. The people at Large Scale Biology say that eventually, they may be 
able to produce a customized drug for a patient in six weeks, and to do it 
thousands of times a year.

"My ideology is that personalized medicine, from the standpoint of strictly 
business, can be just as profitable as the non-personalized type," Erwin 
said. "But most people won't believe that until you can put the numbers in 
front of them."

Erwin's curious plants, hundreds of them, were growing on a greenhouse 
bench in western Kentucky not long ago. On one bench, the specimens of 
Nicotiana benthamiana were making fragments from the tumor of a 58-year-old 
woman from Mill Valley, Calif. Plants on the opposite bench were growing 
tumor fragments from a 57-year-old man from Hollister, Calif.

Awakening a Germ Fighter

Most people think of a vaccine as a drug given ahead of time to induce 
immunity to a germ. That's accurate, but the term is really broader and can 
be applied to many drugs designed to attack disease by inducing an immune 
response.

For years, scientists have theorized that certain types of cancer might be 
particularly amenable to treatment with vaccines. By definition, a patient 
has cancer because his or her immune system has failed to recognize and 
kill cells growing out of control. What if the immune system could somehow 
be awakened to the threat and rallied to attack?

The technical details have bedeviled scientists, however, and no cancer 
vaccine has ever reached the market. But lately, the idea has been showing 
promise for the deadly skin cancer melanoma. And perhaps the most 
impressive data have been gathered in efforts to treat lymphoma, a cancer 
in which a type of immune cell called a B cell grows out of control.

The father of these efforts, Stanford University researcher Ronald Levy, 
more than a decade ago reasoned that lymphoma cells, more than most other 
types of cancerous cells, could be specially susceptible to vaccines. They 
have unique regions on their surface that are different from patient to 
patient but identical on one patient's cancer cells. In theory, a person's 
immune system could be trained to hone in on these regions as targets and 
kill the cells.

Using painstaking laboratory techniques, Levy and his disciples have been 
making customized, experimental vaccines, patient by patient, and giving 
them to people for years. Generally, these vaccines are made using copies 
of the unique region from a lymphoma cell along with substances that tell 
the immune system to recognize the region and mount an attack.

By now, hundreds of patients have been treated worldwide. The results are 
still preliminary, but by the standards of cancer treatment, they are 
remarkable.

About half the patients receiving a vaccine mount a strong immune attack on 
their cancer, and many of these people appear to live for years longer than 
would be expected using conventional treatment alone.

The data are so promising that the National Cancer Institute, under the 
leadership of a former Levy student named Larry Kwak, has recently launched 
a large, definitive test of the approach. Some experts doubt the labor-
intensive manufacturing technique Kwak is using can be scaled up to treat 
thousands of patients, but at least one company intends to try.

Yet other companies think they can streamline and speed up the vaccine-
making process using alternate, potentially cheaper techniques. One of 
these, Genitope Corp. of Redwood City., Calif., has mounted its own large 
test, but acknowledges its technique can take six months to produce a 
vaccine.

Lymphoma is a slow-growing cancer and patients may well be willing to wait 
that long, but Large Scale Biology is betting that they and their doctors 
will want to move more quickly. That's where the tobacco plants come in.

A Virus Harnessed

Large Scale Biology has spent years working on techniques that will allow 
it to produce potentially useful proteins in plants, especially tobacco. 
Like some other companies, including one in Virginia called CropTech Corp., 
the company uses tobacco because its long cultivation has produced a 
hundred-year body of knowledge about the plant.

After hooking up with Levy, the company started making lymphoma vaccines in 
1999 and has tested the safety of the approach in 16 patients. It has won 
permission from the Food and Drug Administration to begin larger trials 
this fall, involving perhaps 250 lymphoma patients.

The technique does not involve genetic manipulation of tobacco plants, but 
rather of a virus that infects those plants.

Genetic material from a patient's tumor is inserted into copies of the 
virus, called the tobacco mosaic virus, and particles of it are sandblasted 
onto tobacco plants. They infect the plant and take over the genetic 
machinery to crank out viral proteins -- including the newly inserted human 
tumor gene.

Ultimately, all tobacco compounds are discarded, leaving millions of copies 
of the tumor protein. The protein is mixed with immune-stimulating 
substances to create a highly tailored vaccine for one patient.

No one is sure what a course of vaccine treatment will cost, but people 
working in the field give rough estimates of $20,000 to $50,000.

That may sound high for what amounts to a series of shots. But most 
insurance companies now will pay upwards of $100,000 for bone-marrow 
transplants for lymphoma patients, a last-ditch treatment. If researchers 
can suppress lymphoma in half or more of patients for less money, 
"insurance companies may actually like it," said Kwak, the National Cancer 
Institute researcher.

He does worry that companies like Genitope and Large Scale Biology may be 
pushing ahead too fast, and could have problems with the potency of their 
vaccine. Levy, the Stanford doctor, is taking a more agnostic approach, 
hoping one company or the other gets the vaccine strategy to work on a 
large scale.

He sounded tickled at the idea that it might happen in the very plant that 
causes an epidemic of lung cancer and other diseases in the United States.

"The idea of using tobacco to make a treatment for patients would be 
terrific," he said.

Environmental Concerns

Around the country, projects in which companies want to use genetically 
manipulated plants to grow human drugs are moving forward. But 
environmental groups have begun to sound an alarm about the potential for 
unintended consequences, especially if the drugs are grown in food plants, 
as some companies intend.

"Just one mistake by a biotech company and we'll be eating other people's 
prescription drugs in our corn flakes," said Larry Bohlen, director of 
health and environment programs at Friends of the Earth, in a recent 
statement.

Quietly, grocery manufacturers have been raising similar concerns in 
Washington. The two main federal regulatory agencies, the Agriculture 
Department and the Food and Drug Administration, have told Congress that 
they are on top of the situation but also have been working to bolster 
their guidelines for industry.

"The potential benefits of the technology are so great that we can't risk 
losing them by not having a regulatory system in place," said Michael 
Fernandez, director of science at the Pew Initiative on Food and 
Biotechnology, a Washington think tank.

Out in the farm fields of Kentucky, the concerns are at once more prosaic 
and more urgent.

Tobacco is a vital cash crop there, as in many parts of the country, 
producing a quarter of farmers' income on 1 percent or 2 percent of their 
land. But the crop is declining, and hard-pressed farmers are left to 
wonder what will take its place.

Danny Ebelhar is one of them. He sat in an equipment shed on his farm the 
other day, cocking his John Deere cap and explaining how he got involved 
with Large Scale Biology, growing test plots of tobacco. These are 
unrelated to the company's lymphoma vaccine, but play a role in its longer-
term plans to produce other drugs.

Ebelhar, one of the county's leading farmers, is trying to hold together a 
solid operation to pass along to his son. He doesn't expect that 
cooperating with outfits like Large Scale Biology will ever produce more 
than 5 percent or 10 percent of his farm income, but he sees it as a way to 
give tobacco a new lease on life.

"It really wasn't a hard sell for these guys to convince us to start with 
them," he said.

His neighbor, tobacco and cattle farmer Rod Kuegel, is also cooperating 
with the company. He's equally realistic about the potential profits, but 
he sees another benefit:

"I thought it would be nice to be on the politically correct side of 
tobacco for once."


*****

for more detailed information read
http://www.aenews.wsu.edu/July02AENews/July02AENews.htm



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