Biologists were experimenting with ways to rev up the body's immune system to fight cancer even back when Jacque Schweiss was born, in 1923...
Biologists were experimenting with ways to rev up the body’s immune system to fight cancer even back when Jacque Schweiss was born, in 1923.
But only now, as the 82-year-old Schweiss wrestles with prostate cancer, has the science advanced far enough to potentially save his life. Last year he took an injection of an experimental, genetically modified virus to galvanize his immune system against his cancer.
These vaccine-style cancer treatments have not been proved to work in large numbers of people. But dozens of companies, including two biotechs in Seattle, are in a race to perfect the technology, and a few suggest they could deliver as soon as next year.
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Despite what the name might suggest, these cancer vaccines do not prevent the disease. Instead, they stimulate the immune system to attack a cancer that is already creating havoc. Studies show they may extend lives by just a few months beyond standard treatments. But they have much milder side effects than the conventional cancer-fighting tools of surgery, radiation and chemotherapy — sometimes known as “slash, burn and poison.”
One of the Seattle companies in the hunt, Dendreon, has a chance to be first in the world to bring a cancer vaccine to market. Mitchell Gold, the company’s brash chief executive who isn’t modest about the company’s goals, often tells investors, “We believe we can fundamentally change the way cancer is treated.”
The treatments also could put new pressure on the health-care system, because cancer vaccines would carry sky-high prices — possibly 10-fold higher than those of existing cancer drugs.
Cancer is now the No. 1 killer in America, causing 570,000 deaths each year, according to the American Cancer Society. One in two American men, and one in three women, will get cancer in their lifetime, according to the National Cancer Institute.
Schweiss, a grandfather, garage tinkerer and retired Lutheran minister from Shoreline, was diagnosed in May 2004. His was a moderately aggressive form that had not spread yet. He was given a 50 percent chance of living five years.
He had three options: standard radiation; radiation plus hormones that amounted to chemical castration; or an experiment involving the cancer vaccine. The experiment called for radiation and a virus genetically modified to penetrate cancer cells and provoke an immune response. His doctor at Virginia Mason Medical Center suggested the third option, developed by California-based Cell Genesys.
Schweiss went for it. The idea was intriguing, and he wanted to avoid side effects of hormones.
The experimental treatment involved six injections into his prostate. They carried a virus engineered to aim exclusively for cancer cells, replicate inside and cause cells to burst. Since the virus is also a foreign invader, the theory goes, it may provoke the immune system to mount a localized assault.
The procedure was over in one 20-minute visit. For extra kick, Schweiss went through 34 days of follow-up radiation zaps into his prostate, which left him tired.
A year later, his energy has returned. He’s back at his hobby of designing pendants in his garage. A recent letter from his doctor said his PSA score, a measurement of cancer in the blood, had decreased seven-fold to a much healthier level.
As long as he doesn’t relapse, Schweiss said, he’s looking to the future. He’s considering another trip, his fourth, to the Holy Land.
“I have friends who went the other routes [with prostate cancer] and three or four years later, they are still having difficulties,” Schweiss said. “I don’t have that. I’m pleased as punch.”
The field of cancer vaccines was once written off by oncologists as fantasy. As far back as the 1890s, a New York surgeon injected live bacteria into patients with cancer. He saw a few isolated cases of tumor shrinkage and some patients who lived longer than expected. The work stalled years later when others were unable to reproduce the effect.
Researchers now say there are many fundamental hurdles any cancer vaccine must overcome. Scientists know the immune system is hard-wired to attack “foreign” invaders, like viruses, while withholding its firepower against healthy tissues. In immunology, the concept is known as “tolerance.”
To be successful, a cancer vaccine must coax the body to overcome its natural tolerance. One way is by helping the immune system distinguish between normal cells and cancerous ones.
There is, however, a trick. Cancer cells differ from healthy ones in subtle ways, enabling them to escape surveillance of the immune system. Through years of experiments, scientists have found that cancer cells have many unusual protein markers — known as antigens. Once such a target is clearly identified, the thinking goes, cancerous cells should be easier to hit.
In reality, it’s not so easy. Many of those proteins involve ordinary cell growth and differentiation. Rapidly multiplying cancer cells have more of those markers, but they are also found in normal tissues.
“That’s one of the things so confounding about cancer,” said Darin Weber, a biotech consultant and former FDA reviewer of cancer vaccines. “There’s a fine line between normal and abnormal.”
Many immune-stimulation techniques have been tried and failed over the last decade.
One technique from the 1980s and ’90s involved chopping up a patient’s tumor in a blender-type device. The idea was to disable the cells, and re-inject them as “unmasked” cancer cells to trip alarms with the immune system. Researchers have also pumped in disabled cancer proteins from other people and put them into a stew with potent immune-system boosting compounds. Neither approach has worked.
Some newer techniques are showing signs of promise. One treatment from Dendreon, called Provenge, zeroes in on a single protein marker to help the immune system spot precisely what it should attack. The protein is made through genetic engineering and mixed with a patient’s own immune-system cells to teach those cells to recognize and destroy it.
Xcyte Therapies, another Seattle company, has a far different philosophy, a shotgun approach to attack multiple protein markers. It uses an incubation process meant to jolt a patient’s T cells, a key part of the immune system, out of a disease-induced slumber. The process also multiplies T cells by the billions. The thought is that those “activated” T cells will do their job of destroying invaders, as they do in a healthy person’s immune system.
Dendreon is further along in development than Xcyte, but human test results for both companies’ techniques have been mixed.
In one Provenge study of 127 patients who failed on other treatments, Dendreon was unable to show it can slow down prostate cancer.
Still, the study showed after three years of follow-up that 34 percent of patients taking Provenge were alive, compared with 11 percent who took a placebo. A second study also failed to reach its main goal, but the follow-up survival results are expected this summer.
If it shows a similar survival edge, Dendreon hopes to apply for Food and Drug Administration approval to sell Provenge next year.
One small Xcyte study showed it significantly shrank cancerous lymph nodes and spleens in leukemia patients but could not stop the cancer cells circulating in the blood. The company hopes to show better results in another trial by combining its activated T cells with another drug. That outcome could take awhile — the trial is now on hold, as the company tries to satisfy questions from the FDA.
The economic cost of cancer in America was more than $190 billion in 2004 when factoring in direct medical costs and lost productivity, according to the National Institutes of Health. Cancer is such a widespread disease that Amgen became a multibillion-dollar biotechnology company largely by treating one secondary issue, the side effects of chemotherapy.
Seventeen cancer vaccines are now in the final stage of clinical testing, according to a survey by Arrowhead Publishers, a market research firm; targets include cancers of the skin, prostate, colon, breast and pancreas. Assuming some earn FDA approval, it forecasts a $6 billion cancer-vaccine market emerging by 2010. Over time, cancer vaccines could rival the U.S. market for chemotherapy, estimated at about $10 billion a year, according to health-care consulting company Broadlane.
If they are shown to work, cancer vaccines are bound to be expensive, much more so than chemotherapy. Taxotere, a common chemotherapy drug, can cost roughly $3,500 per patient after several cycles. Xcyte Therapies says its process can cost $4,600 per patient in raw materials alone, meaning the final price would be several times higher.
Dendreon has not said what it would charge for Provenge, but David Urdal, its chief scientific officer, said the treatment will be priced “up there” with new-generation cancer drugs like Genentech’s Herceptin or Avastin. Avastin, which chokes off blood supply to cancer cells, can cost $40,000 per patient and up.
Dendreon will be motivated to set the bar high. It has been in business 13 years, has no products for sale and has spent more than $200 million of investors’ money.
If it could charge $40,000 per patient, and become the last-ditch treatment for up to 30,000 men who die from prostate cancer each year, sales could top $1 billion a year. Even more money could flow in by using Provenge in milder prostate cancer, which strikes 230,000 American men a year. Dendreon also has a breast-cancer vaccine in clinical testing.
Over the usual 20-year life cycle of a drug, Provenge’s price would likely come down as competitors surface, Urdal said. But he warned that any effort to control prices could stall research and development. “How we as a society solve this issue will have a huge impact on what treatments we’ll have for our kids and grandkids,” Urdal said.
The price of cancer vaccines, if they reach the market, will surely create tension. Medicare, which is expanding to buy more drugs, is pressuring biotech drugmakers to either justify their high prices or lower them.
Scott Ramsey, a health economist at the Fred Hutchinson Cancer Research Center, said the true cost to the health system could be much higher than the price alone suggests. That’s because vaccines could potentially be given periodically as boosters if patients live longer, as add-ons to existing therapies and in larger numbers of patients with milder cancer.
That translates into higher health-insurance premiums for all and puts a responsibility on doctors to use the therapies judiciously, Ramsey said.
“It’s going to increase the lifetime costs of treating cancer patients tremendously,” he said.
Before any such revolutionary change occurs, there will be big logistical barriers to overcome — vaccines are not as simple to give as a pill. Provenge production requires a delicate dance of sterile incubation, speedy long-distance shipping of refrigerated cells, and several doctor visits.
Physicians might not adapt quickly to the technology. Questions linger over whether cancer vaccines using human cells can be consistently manufactured. If a patient ever was harmed by a mix-up, such as by receiving another patient’s vaccine, the fallout could be devastating.
Investors, and patients, have also grown leery of biotechs that promise, then fail to deliver. In 2000, a Dendreon executive told the Wall Street Journal he hoped to start selling Provenge by fall of 2002.
Even as the companies move toward the end of clinical trials, investors remain skeptical of cancer vaccines. They have reasons. Last month, CancerVax of Carlsbad, Calif. halted a trial in the final stage when it appeared to show little benefit for patients with a severe form of melanoma. Its stock fell from $6 to $3 overnight.
The Seattle companies can relate to the pessimism. Xcyte went public a year ago at $8 per share; it is now worth less than $1. Dendreon’s stock is down almost 50 percent this year, in a stretch when the Nasdaq Biotech Index is down just 12 percent.
There are still many scientific challenges vaccines must surmount. For instance, if the immune system is aimed at too many targets, some scientists say it could end up attacking healthy tissues, possibly causing autoimmune diseases, such as rheumatoid arthritis. So far, that hasn’t become a problem in clinical trials — no vaccine has proved that potent.
More often, researchers run into the opposite problem, treating cancer patients who have undergone several rounds of chemotherapy, which has decimated their immune systems. That, it is believed, can make it difficult to re-awaken the immune system’s punch.
Even when fully riled up, vaccines have not shown they can overwhelm large, fast-growing tumors. Dr. Nora Disis, a cancer-vaccine researcher at the University of Washington, said the best odds are in treating patients with milder forms of disease and preventing relapses after chemotherapy.
Disis is optimistic about a different approach that she thinks may help those patients with milder forms of disease. The method involves injecting small snippets of cancer-related proteins after removing the bulky parts that help camouflage cancer from the immune system.
Using that technique, Disis said, it’s possible vaccines can trigger long-term immune-system memory against cancer. In the future, she said, a vaccine given early in life may even prevent the disease.
“It could be a kind of permanent protection,” Disis said. “You could literally have an anti-tumor response going on in your body and not even know it.”
The catch? Any clinical trial to prove the concept would need to follow patients for many years, to see if the vaccine truly provided lifelong protection. Few investors would be willing to wait so long.
Weber, the former FDA reviewer, said there are still plenty of unanswered questions with cancer vaccines. But he takes the long view, and he’s optimistic the research will lead to improved cancer treatments.
“Out of a lot of these failures, do come nuggets of wisdom the next generation can build on,” Weber said. “We’re getting close to the end-game.”
Luke Timmerman: 206-515-5644 or firstname.lastname@example.org