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Vaccines usher in new season of hopeBy CAROLYN POIROT


Cancer researchers are on a search-and-destroy mission to fight the deadliest and most difficult-to-treat cancers.

And the latest weapon in their arsenal: vaccines.

Scientists are using vaccines on two fronts: One approach prevents cancers from developing, similar to polio or flu vaccinations; the other treats already existing cancer by strengthening the immune system’s ability to recognize and get rid of cancer cells.

Researchers predict that some cancers will become vaccine-preventable diseases in the next few years.

“We are seeing a shift in how we look at advanced cancer,” says Dr. Philip Arlen, director of the Clinical Research Group at the National Cancer Institute in Bethesda, Md. “In the past, if we couldn’t remove it with surgery or burn it out with radiation, we had to turn to chemotherapy. ... If we can keep cancer in check with therapies which have very limited toxicity that’s a big step forward.”

About 140 therapeutic vaccine trials are now under way at 20 cancer centers throughout the country, Arlen says.

Immune therapy, which uses various kinds of vaccines including some developed from cancer cells of individual patients, is in early clinical trials for melanoma, leukemia, lymphoma and myeloma as well as malignant tumors in the brain, breast, lung, kidney, ovary, prostate, pancreas, colon and rectum. Some of the trials have had initial success. Consider:

In Houston, researchers are studying a vaccine developed from each patient’s own activated lymphocytes to fight malignant melanoma.

Last week, a federal advisory panel recommended that the U.S. Food and Drug and Administration approve the first vaccine, designed to prevent cancer by preventing the virus that causes cervical cancer, the second-leading cancer killer among women worldwide. A second vaccine against the human papillomavirus, or HPV, which causes most cases of cervical cancer, could be approved by the end of the year.

And a vaccine is already widely available to prevent hepatitis B, which causes 70 percent of all liver cancer.

Dr. John Nemunaitis, an oncologist at Mary Crowley Medical Research Center in Dallas, developed the first effective vaccine to combat small-cell lung cancer — the No. 1 cancer killer among both men and women in the United States — and is testing it against other forms of cancer.

The vaccine works by exposing cancer cells in such a way that the body’s own immune system can hunt them down anywhere in the body and destroy them with no harm to normal cells, much the way the immune system normally rids the body of colds, flu and other viruses.

“The fact is, our own immune systems are capable of dealing with widespread cancer without too much trauma,” Nemunaitis says, noting the side effects of his vaccine “are like those you would have with a flu shot, mostly mild irritation at the injection site, maybe a little fever.”

His trial, published in the Journal of the National Cancer Institute in February 2004, opened the door for vaccines to revolutionize cancer treatment.

Chemotherapy vs. immune therapy

If chemotherapy keeps his cancer on hold long enough, Paul Needham would like to try a vaccine to get rid of his pancreatic cancer — once and for all.

Needham, 84, volunteered for a cancer trial at Mary Crowley Medical Research Center hoping to get the experimental vaccine, which is awaiting FDA approval. The vaccine uses a patient’s own tumor cells to help the immune system recognize and get rid of the cancer.

“I got into it hoping and praying I would get the vaccine. . . . It’s more on the leading edge than anything else I could try,” says Needham, a Dallas financial planner.

Needham is now part of an ongoing study comparing immune therapy to the best available standard treatment. In Needham’s case, a computer “coin toss” assigned him to the chemotherapy control group.

“Most of our patients are late-stage cancer patients by definition,” says Nemunaitis, who directs the study. “Our trials are mainly open for patients with advanced cancer, patients for whom initial treatments have failed.”

The problem, in many cases, is that by the time patients qualify for an experimental trial, earlier treatments have severely weakened their immune systems, damaged vital organs or left them anemic.

Needham had to abandon his initial chemotherapy regime because of life-threatening side effects that included a low white blood cell count and low platelets.

“I first took a combination of two drugs, one experimental. It was very effective at shrinking the tumors, but it wasn’t very good for the rest of my body,” Needham said during a recent visit to Mary Crowley to discuss blisters that had developed on his feet with the latest drug.

“In a way, it’s a good side effect, because it means your body is sensitive to the drug and we can lower the dose,” said Nemunaitis.

In clinical trials, vaccines are being used alone, in conjunction with radiation and chemotherapy and with “biological response modifiers” that help boost, direct or restore the patient’s natural ability to fight disease.

The idea is to get the immune system to attack tumor cells that it would otherwise not recognize as invaders, says Neil Senzer, an oncologist who works with Nemunaitis at Mary Crowley, located at Baylor University Medical Center in Dallas.

“Cancer cells hide from your immune radar, and we have to uncloak them so the immune system can find them, like a stealth bomber. The best thing is, there is no toxic reaction. The vaccine doesn’t destroy any good cells, so you don’t get toxic side effects. It doesn’t make you sick,” Senzer says.

First successful vaccines

Two drug companies have developed vaccines to prevent infection with the human papillomavirus or HPV, which causes cervical cancer. Both have passed clinical trials with stunning results.

“HPV vaccine prevents cervical cancer because it prevents the viral infections that cause the cancer,” says Dr. Jayanthi Lea, assistant professor of obstetrics and gynecology and an HPV researcher at Southwestern Medical School in Dallas.

One of the vaccines, Merck’s Gardasil, was 100 percent effective against the development of precancerous lesions in a two-year study of 10,000 women, while a longer study, published just last month, found that more than 98 percent of the women who got GlaxoSmithKline’s Cervarix still had protective antibodies against HPV 16 and HPV 18 more than four years after they were vaccinated.

Earlier this month, a federal advisory panel unanimously recommended that the FDA approve Gardasil for sale in the United States, and approval is expected by June 8. GlaxoSmithKline has not yet submitted its vaccine for marketing approval, but says it too could be in doctors’ offices within a year.

In the United States, 9,710 women will be diagnosed with cervical cancer this year, and 3,700 will die from it, according to the latest data from the American Cancer Society.

The number of women diagnosed with the disease has been dropping in the U.S. because of widespread screening with Pap smears, which can detect pre-cancerous lesions before they become invasive.

However, about 270,000 women die of cervical cancer worldwide each year, and that number is expected to jump to 1 million by 2050 because of the prevalence of sexually transmitted HPV and the lack of Pap smears.

Merck is recommending that girls as young as 9 and women up to age 26 be vaccinated.

“There is already some opposition because HPV is a sexually transmitted disease, but it is very widespread,” Lea says. “The majority of people [who are sexually active] carry around the virus and don’t realize it’s there. . . . Your body can spontaneously get rid of it or it can take hold and cause cervical cancer. With advanced cervical cancer, survival rates are poor and recurrence rates high, and when it comes back, it is almost always fatal.”

Lea says it’s crucial to get the vaccine to young people before they become sexually active: “We want to get to the population at risk of contracting the disease, the earlier the better.”

Building immunity

Malignant melanoma is an important target for scientists looking for ways to use vaccines to mobilize, strengthen and train the body’s own immune system to fight cancer.

“We are targeting melanoma because it is such a tough cancer to treat, and it affects so many young people,” said Dr. Patrick Hwu, chair of the M.D. Anderson Cancer Center’s Department of Melanoma Medical Oncology. “If we catch it early, it can be cured, but if it’s spread to lymph nodes, it can come back at any time — five, 10 or 20 years down the road.”

Skin cancer is second only to leukemia in the number of deaths in terms of productive life lost, Hwu said. He was recruited to M.D. Anderson from the National Cancer Institute, where he has worked for more than 15 years on ways to better use vaccines to get a patient’s own immune system to seek out and destroy melanoma cells.

Melanoma rates have been increasing since the 1970s, with 62,190 new cases expected this year. It will kill an estimated 7,910 people, according to the American Cancer Society.

“You can cut out all the lymph nodes, cut out everything, and it still comes back. It can spread to almost any part of the body — most commonly the lungs, liver, bones, skin and brain,” Hwu said in a recent telephone interview. “Chemotherapy does little to extend survival rates.”

The immune system can track down malignant cells anywhere they are hiding.

Melanoma is a good candidate for vaccine therapy because it is one of the most immunogenic cancers, that is, it attracts immune cells, which apparently recognize the malignant cells as foreign invaders, and tries to get rid of them on its own, unlike most cancer cells, which the immune system ignores.

“When we check out melanoma tumors in the lab, we often find lymphocytes, the soldiers of the immune system, are there. The problem is they seem to be asleep, and we don’t know why,” Hwu says.

Hwu is recruiting patients for a study that uses a vaccine developed from each patient’s own activated lymphocytes in combination with high-dose interleukin-2, which allows the lymphocytes to grow and multiply, and dendritic cells — another type of immune cell that alerts lymphocytes to the presence of danger.

Hwu is growing immune cells to infuse back into patients, and plans to begin infusing the first patients in June.

“We are developing more and more rational combinations in scientific ways to make vaccines work better,” Hwu says. “You have to use some sort of combination. Vaccines are good at preventing disease. Smallpox, polio and mumps have all been knocked out by vaccines. The most important medical advances of the last century can be attributed to vaccines, but they work by preventing disease. You can’t take a flu shot after you already have the flu. It may ultimately be unrealistic to use a vaccine alone to treat cancer that has already spread.”

Every day, scientists are learning more about basic immunology — what turns the immune system on and off, how to get it to recognize and destroy cancer cells.

“We know activating the immune system can be quite potent. We can see tumors shrink. It’s really very, very exciting,” Hwu says. “I believe we are on the verge of realizing the immune system’s true curative potential.”


How to participate in clinical trials

Patients interested in participating in a clinical trial of a cancer vaccine should talk with their doctors and contact the National Cancer Institute at (800) 4-CANCER (422-6237) or at www.clinicaltrials.gov.


Carolyn Poirot, (817) 390-7687


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