Vaccine Could Fight Melanoma
Peggy Maddox’s life was saved by a movie and a cancer center named after a movie star.
Maddox found a lump under her arm in the summer of 1983, a swollen lymph node characteristic of melanoma--the most deadly form of skin cancer. Surgeons near her Redondo Beach home removed the lump and pronounced her cured. By fall, she thought she had another lump, but the surgeons told her she was wrong, that she was OK. She accepted their verdict--until she went to see “Terms of Endearment,” in which a young mother dies of cancer. “That’s when I decided to go for another opinion,” she said. “You don’t want to be looking for more cancer when you are coming to the point you are healthy and whole. But my inner voice told me to go.”
The second opinion confirmed her inner voice. This time, for treatment she went to Dr. Donald L. Morton at what was then the Wayne Cancer Clinic at UCLA. Morton removed 60 lymph nodes from her neck and under her arm and found that 16 contained cancer cells, a frighteningly high number. “He gave me a 2% chance for survival and a couple of months to live,” Maddox said.
Maddox, a continuing education teacher for nurses, volunteered for an experimental treatment program Morton was beginning. In September 1984, he injected her with a melanoma vaccine composed of laboratory-grown melanoma cells “defanged” so they could not reproduce in her body.
The vaccine stimulated her body to fight off the melanoma cells that remained behind, and she beat the odds. Today, she goes in every six months for a dose of the vaccine and a checkup, but she remains healthy and, more than a decade after her recurrence, is classified as cured.
Maddox was the first in a long line of melanoma patients who have had their lives extended by the vaccine developed by Morton, now president and medical director of the 4-year-old John Wayne Cancer Institute at St. John’s Hospital and Medical Center in Santa Monica.
Morton and his colleagues have pioneered some of the most innovative treatments for melanoma. They devised the so-called “sentinel lymph node” test for determining if melanoma and some types of breast cancer have spread--a technique now in clinical trials around the world.
They also developed the still-experimental cancer vaccine that has proved remarkably successful in treating melanoma patients whose cancer has spread to other parts of the body, a group that normally has very limited prospects.
Morton recently reported results from preliminary trials of the vaccine on 136 patients, comparing them to 1,203 Wayne melanoma patients who received standard treatments, including chemotherapy and surgery.
Fully 26% of those who received the vaccine survived five years or longer, compared with only 6% of those who received standard therapy. Among those given standard therapy, the average survival time was 7.2 months. Those who received the vaccine survived more than three times as long, an average of 23 months.
With support from the National Institutes of Health, Morton and his colleagues are now gearing up for a full-scale, double-blind clinical trial of the technique at 20 centers nationwide. If those trials are successful, Morton said, the vaccine could be in routine use in as little as five years.
“This is a step in the direction of increasing the life span of patients who are quite ill with the disease,” said biologist Ralph Reisfield of the Scripps Research Institute. “It’s a big thing” if that can be done, he said.
The team is readying similar trials of the vaccine against breast, lung and kidney tumors.
But despite its low profile, the Wayne Institute has grown to be the second-largest melanoma center in the world and the second-largest cancer center on the West Coast.
“It’s the best-kept secret in Los Angeles,” said Michael Wayne, son of “the Duke.”
More than 600,000 Americans develop skin cancer each year, primarily as the result of excessive exposure to sunlight. Most of those cancers are highly curable “basal cell” or “squamous cell” tumors. But about 32,000 of them will be the highly deadly form called malignant melanoma.
About 8,800 people will die of skin cancer this year. The great majority of the victims, 6,700 people, will die of malignant melanoma, even though that form accounts for fewer than 5% of all skin cancer cases.
Melanoma has been a lifelong interest of Morton, who says he “grew up at a time when the culture was that to be tanned was to be beautiful.” Now, he says, society is suffering the aftereffects of that misguided perception.
He began thinking seriously about a vaccine when he observed that melanoma “spontaneously goes away sometimes,” suggesting that the body’s immune system can successfully attack it under the proper circumstances. He has been working on a vaccine “for 30 years--unfortunately, 20 of them unsuccessfully.”
But his treatment is not a vaccine in the conventional sense, one that keeps a person from developing the disease. “We’re probably not going to see that in my lifetime,” he said.
Instead, as is the case with most vaccines for cancer and AIDS, his treatment is designed to bolster the immune system and help it fight off an existing disease, a task that most researchers feel is much simpler than developing a preventive vaccine for such complicated diseases.
The key to cancer vaccines is the fact that most tumor cells have proteins on their surfaces, called antigens, that are different from the antigens on a body’s own cells. Theoretically, the immune system should be able to recognize these antigens and destroy the cells bearing them.
In the real world, however, it often doesn’t work that way. In most cancer victims, the immune system does not respond strongly to the tumor antigens. Researchers believe that the tumor cells either mask the antigens or secrete a chemical that interferes with immune function.
The purpose of a vaccine is to present the body with readily recognizable antigens, thereby inducing it to mount a stronger immune response.
After many false starts, Morton ultimately put together a vaccine containing cells from three separate melanoma cell lines grown in the laboratory. Cells from those three lines display 10 antigens commonly found in melanomas.
The cells are treated with X-rays so that they cannot proliferate; then they are combined with another immune system stimulant called BCG--a weakened form of the tuberculosis bacterium--before being injected into patients. The primary side effects are a slight fever, a rash at the injection site and occasional diarrhea for a day or so after the injection.
Several other researchers are developing their own melanoma vaccines. Dr. Steven Rosenberg and his colleagues at the National Cancer Institute have extracted white blood cells from melanoma patients, cultured them in the laboratory to vastly increase their numbers and injected them back into the patients with some success.
Researchers at the Memorial Sloan-Kettering Cancer Center and the Mt. Sinai Cancer Center in New York City are using genetic engineering techniques to produce large quantities of tumor antigens, which are injected into patients without having to expose them to the rest of the tumor cell.
Morton, naturally, favors his own approach.
“We tried using the patient’s own cells, but we found it wasn’t practical,” he said. “It took too long to grow them, and the cost would be prohibitive. It would be close to the cost of a bone marrow transplant and would break the back of the health care system.”
And there has been a big debate in the field about the relative merits of living-cell and tumor-antigen vaccines, similar to that which surrounded polio vaccines 30 years ago. Ultimately, it has become clear, he said, that living cell vaccines such as the Sabin polio vaccine provoke greater immunity than antigen-based vaccines such as the Salk vaccine.
“But there are lots of problems with living cells,” he added. “Most people didn’t think a living cell cancer vaccine could be standardized to get FDA approval. Proteins are much easier to work with.”
Critics contend, however, that living-cell vaccines carry the risk that some cells in the vaccine will not be disabled, leading to a vaccine-induced cancer. Or, they say, the disabled cells may somehow regain the ability to multiply.
Workers at the institute are renovating a second-floor laboratory to FDA specifications so that the research team will have enough space to make the vaccine for the forthcoming trial.
Morton, who is confident about the effectiveness of his vaccine, said he loses sleep at night because half the patients in the forthcoming trial will receive only a placebo--a simple salt solution--instead of the vaccine. “But there is no other way the FDA will accept the vaccine without doing a trial,” he said.
The qualms and second thoughts about giving a placebo to patients who could be helped by the vaccine are part of the price of being a researcher, he said. “Unless you are willing to have your work subjected to the scientific discipline of clinical trials, you should be in private practice treating everybody by intuition.”
