One good use for tobacco

[john]

An Idea Is Planted: Firm Uses Tobacco to Grow Cancer Drugs

The tobacco seedlings reaching toward the bright sunlamps in an indoor

greenhouse look fairly ordinary. But the young plants growing in this rural

nursery aren't destined to become cigarettes.

Inside their broad, green leaves, the plants are pumping out bits of cancer

tumor as they spread upward in the 80-degree warmth. In a laboratory nearby,

the tumor fragments will be wrung from harvested plants and used to make an

experimental biotechnology vaccine.

So far, 16 people with non-Hodgkin's lymphoma, an incurable cancer of the

lymphatic system, have received this vaccine produced by Large Scale Biology

Corp. One patient was a 29-year-old mother of two; another was a 12-year-old

boy. Each received a vaccine that was not mass-produced but customized to

attack his or her specific tumor, a step toward the long-promised era of

"personalized medicine." Lymphoma spreads slowly, so it will be years before anyone

can be sure that the vaccine works. But the early signs are encouraging. At a

medical conference in Philadelphia last week, Large Scale Biology reported

that 10 of the 16 patients made tumor-fighting white blood cells after getting

the shots, a large percentage for a cancer drug.

Much is riding on Large Scale's vaccines -- both for cancer patients and for

the company. After raising $89 million from an initial public stock offering

in 2000, Large Scale has 12 to 18 months of cash remaining. The cancer

vaccine is one of two drugs the company is feverishly developing. And with its

shares hovering in penny-stock territory, time is running out for the company --

though it wouldn't be the first biotech firm to roar back from the edge.

All current biotechnology drugs approved by the Food and Drug Administration

are made by gene-splicing bits of DNA with live cells -- usually hamster

cells -- and turning them into mini-cell factories to produce a specific drug.

But Large Scale's scientists believe that a vaccine created through plants

might be purer and avoid copying defects found in mammals. Large Scale chose

tobacco because it is cheap and grows rapidly, a promising vehicle for producing

many small batches of vaccine at an acceptable price.

Next month, Large Scale hopes to persuade the FDA to approve a more

elaborate human test of its lymphoma vaccine on 280 patients. Yet even if the company

gets that go-ahead, it must raise an additional $50 million to fund the

trials, which could take four years to complete.

The founder of Large Scale is 48-year-old Robert L. Erwin, an earnest,

rail-thin biologist with a very personal grudge against cancer: It killed his

first wife in 1994 after agonizing surgeries, radiation treatments and

chemotherapy. From the window of his Vacaville office at Large Scale, Erwin can see the

sprawling $500-million factory where South San Francisco-based Genentech

Inc., the world's second-largest biotechnology company, makes its breast cancer

drug Herceptin. The drug combats breast cancer cells and might have saved his

wife, Marti, but she died while it was in development.

The loss of his wife drove Erwin to find a way to slash development times

for cancer medications to weeks instead of years. Large Scale says it now can

develop a vaccine for a patient in six weeks and hopes to eventually produce

enough custom vaccine to treat 10,000 patients each year.

"One thing I've learned," said Erwin, "is that speed is important for some

patients.The vaccines produced by Large Scale differ from shots given to

healthy children to protect them from measles or chicken pox. People who get a

lymphoma vaccine already are sick, in part because their immune systems failed

to notice or sufficiently fight their tumors.

There are more than 50 biotech vaccines in development against various types

of cancers, but none has reached the market and few are custom-made for

individual patients. Typical is a melanoma vaccine being tested by CancerVax

Corp. of Carlsbad, Calif., that contains 30 different tumor fragments commonly

present in skin cancer.

Many scientists believe that lymphoma requires a personalized approach

because it has substances on the surfaces of its deadly cells that vary from

patient to patient. A vaccine made from these so-called surface antigens could

train a patient's immune system to recognize and fight the cancer, researchers

believe.

Large Scale teamed up with Stanford University scientist Ronald Levy, who

started work on lymphoma vaccines in the late 1980s and who now runs the firm's

first round of drug trials. Levy and his students have treated hundreds of

patients in his Stanford laboratory over the last two decades. A former

student, Larry W. Kwak of the National Cancer Institute, is now a rival and is

preparing to test a personalized vaccine on hundreds of patients in a clinical

trial that could lead to FDA approval.

To this point, Large Scale, in keeping with standard practices, is providing

its cancer vaccine for free as the company conducts its testing, and no one

knows what this kind of treatment might really cost in the end.

Kwak figures it could be as much as $50,000 for a series of five or six

shots. That would be half the $100,000 cost of a bone-marrow transplant -- a last

resort for lymphoma patients -- but 10 times the expense of standard

chemotherapy. Still, insurers may be willing to cover vaccines if the shots allow

patients to avoid years of expensive medical care, Kwak said. Large Scale

believes that it can shave costs by producing drugs in tobacco, an innovative

counterpoint to Kwak's complicated but time-honored technique that involves

fusing a patient's tumor cell with a mouse antibody. Large Scale's president, John

D. Fowler, said the company's production expenses could be 30% lower than

those of biotech firms that use the routine method of making drugs in rodent

cells.

Large Scale uses a natural enemy of tobacco, the tobacco mosaic virus, to

produce its vaccine. The company slips genes from a patient's tumor into copies

of the virus, a virulent bug that is a scourge to farmers. As the altered

virus infects plants, it produces tiny tumor fragments that build up in the

tobacco leaves and stems. Six weeks later, the plants are harvested, washed and

spun in a centrifuge to extract plant juices. The solution is purified and

reduced to an amount of vaccine that wouldn't fill a Coke can. Patients receive

six shots spread over as many months along with other injections to boost

the immune system.

In the company's greenhouse, young plants with yellowing, mottled leaves

grow in neat rows on long, wooden tables. The plants are a cousin of the tobacco

strain grown for commercial use. A team of horticulturists tends the plants,

which are grown from seeds no larger than a pinhead in temperatures that

never dip below 72 degrees.

Lab assistants painstakingly infect the plants by hand, gently scratching

the leaves with a solution containing the virus, which can be transmitted only

by direct contact. It takes 1,000 plants grown to a height of 6 inches or so

to make enough vaccine for a single patient, an amount equal to half a

teaspoon.

Catherine Gallegos, a school administrator in Monterrey County, became one

of the first patients to receive Large Scale's vaccine in May 2001. By then, a

harsh chemotherapy regimen had forced her neck and abdominal tumors into

remission, but doctors warned that the cancer probably would recur.

Gallegos' shots ended a year ago, but her immune system continues to make

anti-tumor white blood cells. To Gallegos, the vaccine offers a chance to break

the inevitable cycle of chemotherapy treatments followed by shorter and

shorter remissions, the deadly hallmark of lymphoma. "It gives me peace of mind

to know that my system is responding," said Gallegos, 57, who lives near Santa

Cruz. "I feel like I have my life back."

Erwin didn't have cancer vaccines in mind in 1986 when he founded the

predecessor of Large Scale. But his first wife's illness sharpened his business

focus. After the standard artillery of surgery, chemotherapy and radiation

failed Marti, Erwin became convinced that a different approach was needed.

Marti's inability to obtain Genentech's experimental drug also transformed

Erwin into a crusader, an unlikely role for a biotech CEO. With his blessing,

fellow activists stormed Genentech's campus after her death in a mock funeral

procession. Since then, Erwin has quietly lobbied pharmaceutical companies

to provide experimental medications to patients whose cancer defies treatment.

Erwin acknowledges that it can be difficult to balance his zeal with his

responsibilities as Large Scale's CEO. His company recently was ready to provide

the cancer vaccine to an additional patient, who didn't technically qualify

for the drug trial, but she did not survive a bone marrow transplant.

However, Large Scale's financial condition doesn't allow it to routinely offer

treatment to others.

In the next few months, if the firm does not find a partner to fund another

round of cancer vaccine trials, the vaccine could be set aside. But it

probably wouldn't sit on a shelf permanently. The company hopes it can license its

technology or possibly try to develop it again later.

"It isn't just about making money," Erwin said. "We're giving patients

something that really matters."