Sticking it to Cancer
A new vaccine, amazingly, may rid the world of cervical cancer, while doctors aim other needles at more killer tumors
A prick against the skin of her upper arm, a quick injection, and Janelle Kitson was protected against a scourge of women: cervical cancer. "It's just like any regular shot, like a flu shot, and people should really take advantage of it," says the 26-year-old from Seattle, who got the needle five years ago as part of a clinical study to see if it works. "I used to tutor some kids, and I think one of the moms had this cancer. She was going through chemotherapy, and it was pretty tough on her."
Kitson now has a good chance to avoid that fate. The shot she got was a vaccine against the human papilloma virus, or HPV. Two types of this virus cause 70 percent of all cervical cancers, which kill 270,000 women worldwide each year, nearly 4,000 of them in the United States. Remarkably, the vaccine prevents infection from these two types 100 percent of the time.
That number has doctors cheering wildly. "It's been a jaw-dropping experience to see protection like this," says Kevin Ault, an obstetrician and gynecologist at Emory University School of Medicine in Atlanta. "Look, I analyzed data from 20,000 patients from five different continents. And we saw complete effectiveness against lesions that could become cancer," says Ault. "When this vaccine is approved, my oldest daughter, who is 9 now, is going to get it."
This is a historic moment: the first real attempt to wipe a cancer off the face of the planet. And in June, the U.S. Food and Drug Administration will play a crucial role in that act of extinction. That's when the agency is set to decide whether to approve the vaccine, called Gardasil and made by drug giant Merck. While approval isn't an absolute slam-dunk, there are few who doubt it will happen. "The data presented to us look very strong," says Janet Gilsdorf, a University of Michigan pediatric infectious disease doctor and a member of the federal Advisory Committee on Immunization Practices, which is working on recommendations about who should get vaccinated and at what age. The anticancer effort is also going global: A second, similar vaccine from rival Glaxo Smith Kline, called Cervarix, was just submitted for approval in the European Union and several other countries three weeks ago. It's headed for the FDA later this year.
Living longer. There are more cancers poised at the tip of the vaccine needle, too. These medications don't prevent cancer from starting but attack tumors that already exist, vanquishing them or at least stopping their lethal growth. One such therapeutic vaccine medication recently showed success against advanced prostate cancer, and it appears to extend patients' lives longer than the best current therapy. Though other researchers worry the studies might be too small to prove anything, the manufacturer intends to seek FDA approval later this year. A different technique--infusing a patient with billions of cancer-killing cells--has also shown some promise in experiments.
What all these cutting-edge treatments have in common is a rejuvenated immune system, ready to stop a deadly foe. In the case of the new cervical cancer vaccine, it works because of the tight link between the cancer and HPV. DNA analysis has revealed that about 15 types of the virus account for more than 99 percent of all cervical cancer cases and that the virus can hijack cervical cells and turn them into growing malignancies. Other types are responsible for another problem, one afflicting men as well as women: genital warts.
Unfortunately, HPV is an annoyingly common germ. About 25 percent of adolescents and young women and men are infected at any given time. It's passed around through sexual contact--and that doesn't mean just fluids but also skin rubbing on skin. Fortunately, the body is pretty good at getting rid of most infections on its own. The virus infects the skin, but skin is constantly shedding cells, so it's constantly dumping the virus, too.
But sometimes it doesn't. If the virus invades skin stem cells--cells at the bottom of a skin layer that constantly divide to replenish the layers above them--it can cause a persistent infection. That can lead to trouble, but not right away. "It takes about one to three years of infection to produce a lesion," says Diane Harper, a cervical cancer specialist at Dartmouth Medical School. "And during that time you don't have any symptoms. But eventually, there will be some abnormal cells." That's a low-grade lesion, and it can hang around for an additional five years, looking more and more unusual. It's still not cancer, though. That transformation can take another five years. "So it could take 13 or so years after initial infection for a true cancer to develop," says Harper. That's why, although the peak infection years are adolescence and the early 20s, most women with actual cancer are in their 30s or older.
Katie Allen was 48 in 1995, when she began spotting blood. "I thought I was starting menopause. Cancer was the furthest thing from my mind," says the Anaheim, Calif., archaeologist. But the flow got heavier after a few months, so Allen made an appointment to see a gynecologist. She was stunned when he called to say she had cancer. "All I could think was: I have cancer, and I'm going to die. I haven't even been getting regular Pap tests. I've killed myself."
Allen opted for a hysterectomy, but during the operation surgeons found that the cancer had spread to lymph nodes in her pelvis. The surgeon took them out, but Allen still needed radiation to zap any malignant cells left behind. The radiation did the trick, but Allen suffered from side effects, such as bad diarrhea, for years. And she had exhaustive, repeated checkups every three months. "But I count myself lucky, because you die from this disease. If there was a vaccine, and my daughter could get it, I'd make her do it."
She and her daughter may be having that conversation very soon. Gardasil is designed to protect against the two most malevolent types of HPV, numbers 16 and 18. It also protects against two types that cause genital warts in men and a few hundred thousand low-grade lesions in women that prompt anxiety and thousands of pelvic exams. "That adds up to a big health expense, so removing it is a big public-health benefit," says Eliav Barr, who runs Merck's HPV clinical testing program. (These checkups and procedures cost between $3 billion and $6 billion per year in the United States.)
The vaccine looks like HPV, but it isn't. It's just an empty shell, made from the protein in the virus's outer coat. But that surface similarity is enough to provoke an immune response.
In fact, three injections of the vaccine, spread over six months, prompt the body to produce antibodies against these HPV types at levels that are hundreds of times as high as normal. Follow-up studies so far show that people maintain these heightened levels for at least 3
Long-lasting. Cervarix, the rival vaccine from Glaxo, is made in a similar way and shows very similar results. The differences: It vaccinates against types 16 and 18 only, and it contains a novel chemical to boost vaccine longevity, perhaps beyond what Gardasil is capable of. "We found that you get the strongest antibody response from kids ages 10 to 14, about twice as strong as older teens," says Gary Dubin, the virologist who heads Glaxo's HPV vaccine program. "So you vaccinate at a young age for the powerful response, but you need it to last." If it doesn't, kids will be at risk as they mature and start to have more sexual contacts. Dubin's group has shown that the strong response extends for at least four years and might last for a decade.
Helen Wright, age 14, of North Augusta, S.C., is taking part in some of these tests and would be grateful for some protection. "At first I was like 'I'm so scared' when I found out about HPV. But then I thought if I'm taking these shots, I might not catch it when I get older."
But nobody knows for sure. "Figuring out the duration of protection is going to be key," says Koutsky. For one thing, it will indicate when vaccinated people will need booster shots. So drug companies and researchers are following a group of people who were vaccinated several years ago, waiting and watching for signs of infection and disease. "Until we know about that, Pap smears are going to continue to be important for women," says Dartmouth's Harper. "Cancer prevention, in the future, is going to require screening as well as vaccines."
Prevention isn't the only goal of vaccines, however. For other cancers, they may work as treatments, like cancer-killing drugs. Prostate cancer, which will kill about 27,000 men in the United States this year, is one target. "I never felt sick, not once," says Harry Petersik, who had prostate surgery 12 years ago because a high prostate-specific antigen test led to the discovery of a tumor. Petersik, a 64-year-old electrician who lives near Edmonton in Alberta, Canada, thought he was out of the woods. But over the years his PSA levels kept climbing, indicating the cancer was back. Other treatments failed. By the start of 2005, the cancer had spread through his lymph system. And he had tumors in his back and shoulders.
The problem in this case--in all cancer cases--is that tumors were evading his immune system, because that system didn't recognize them as foreign invaders. So Petersik turned to a Seattle-based company called Dendreon that teaches old cells new tricks with a therapeutic vaccine called Provenge.
Doctors take cells designed to spot intruders out of the patient's body, juice them with prostate cancer molecules, and put them back in the patient. These cells then point the immune system toward the real enemy. In January, as part of a clinical trial, Petersik lay still for three hours while the vaccine flowed into his body through an IV drip. "I got infused three times," says Petersik. "There had been a large tumor in my lower back. It practically disappeared. And the pain it caused went away, too."
Dendreon recently completed studies of 225 patients like Petersik and found that Provenge increased their survival by nearly 4
Loaded up. Pancreatic cancer is another new target for vaccines. About 33,000 people will be diagnosed with it this year, and almost all of them will soon die. The PanvacVF vaccine, made by a company called Therion in Cambridge, Mass., is a shot in the arm with a benign virus that has been loaded with genes culled from pancreatic cancer cells. The shot gets the immune system to produce cancer-killing cells, and booster shots every few weeks or months keep the reaction going. "We're trying to get the patient's immune system to view the tumor as a bad organ, like an organ transplant, and reject it," explains Therion's Thomas Schuetz, a medical oncologist. So far, in small studies, he's seen vaccinated patients generate a lot more of these tumor-killing cells. Another vaccine, Gvax, is an injection of pancreatic cancer cells along with a molecule designed to attract immune cells and sensitize them to the deadly growth.
But these studies have attracted critics along with hopeful patients. "A lot of these vaccine trials are small, and their response rates are low," says Mario Sznol, a medical oncologist at Yale. "That means some positive findings could simply be due to chance." Steven Rosenberg, chief of the surgery branch at the National Cancer Institute, is more blunt. "There's been a lot of hype here. Most of these trials don't show tumor shrinkage, which is the gold standard of success."
Rosenberg has his own solution, focused on making tumors not just shrink but melt away. He's targeting advanced metastatic melanoma, a disease in which only 16 percent of patients live for five years after diagnosis. A few immune cells, called TIL cells, do attack such tumors, but there aren't a lot of them. So Rosenberg picks them out and grows the most aggressive ones in the lab, multiplying them by the billions. Then he kills off old, ineffective immune cells still in the patient with heavy doses of toxic chemo and replaces them with the new cancer slayers. "They bring your cells back to you, in these bulky plastic bags, and hook up an IV tube," says melanoma patient Jessica Mosher, 31, of Manassas, Va., who first was treated in 2002. What had started as a small spot on her back a year earlier had morphed into tumors in her lungs, her liver, and a huge one in her back. "I knew there were billions of cancer-fighting cells in the bags, and I got more and more excited."
After the infusion, Mosher got doses of a chemical that helps the cells to replicate. A month later she had a CT scan. "Twenty tumors in my lungs were just going away." She has been free of cancer since 2004.
The method is called adoptive cell transfer, and Rosenberg has used it on 35 patients. Half of them saw their tumors shrink, sometimes to nothing. Not everyone is bowled over, however. "A lot of the objections Steve has to vaccines can also apply to adoptive cell transfer," says immunologist Jeffrey Schlom, who works with Rosenberg at NCI. "These are small numbers, prone to bias, and it's not clear how many patients can actually be helped in this way." The treatment is harsh--Mosher ended up on a ventilator at one point--and it's cumbersome and expensive and complex.
Schlom and others also think vaccines are dismissed too quickly. Melting away tumors may be the traditional version of success, he says, but vaccines call for a different definition. "We're talking about controlling disease. We all live with viruses in our bodies, and we control them--we don't eliminate them," Schlom says. "And with vaccines, we're starting to see patients live longer with a good quality of life but little tumor shrinkage. Provenge, for instance, got months of extra survival but no toxicity. That's very exciting." Whatever the method, the goal is to gain good years. "Clearly, we're not there yet," says Sznol. "But I hope, and I think, that we're getting closer."
This story appears in the April 3, 2006 print edition of U.S. News & World Report.