Vaccine Offers Hope in Melanoma Treatment : Made From Malignant Cells, It Is Aimed at Stopping Spread of Skin Cancer
It is the rare moment in a scientist’s career that is punctuated by a resounding “Aha!†The discovery, that crucial piece of the puzzle, the hoped-for results.
In some cases it is the solution to a heretofore elusive mathematical problem. In others, it is unraveling the secrets of a stubborn protein.
For one researcher, cloistered in a seventh-floor laboratory at USC’s Norris Cancer Center, it was leaching cancer-controlling factors from cancer cells themselves, zeroing in on the prototype of an unusual generation of vaccine.
It is not a vaccine in the accepted sense of the word, however, but one made with a mixture of malignant melanoma cells that have been homogenized to release an immunizing material--a substance that boosts cellular immunity by stimulating production of killer “T-cells.†Such cells in turn battle the progression of malignant melanoma, an often vicious and fast-moving skin cancer.
Not a Miracle
“I don’t want to call this a breakthrough,†cautioned Dr. Malcolm Mitchell, who first conceived of the melanoma vaccine in 1984 and who now has approval from the Food and Drug Administration for experimental uses. “This is not a miracle drug.
“I wanted (to develop) something that could be used in large groups of people and was a uniform preparation. Originally, I wanted to use it in people who had just had surgery and (who) had no signs of melanoma at all.â€
What Mitchell has developed is a prototype drug that appears to promote tumor shrinkage in some malignant melanoma patients participating in a preliminary study. A second study is getting under way.
Unlike more traditional vaccines, which are based on viruses, Mitchell’s immuno-therapeutic agent does not prevent the disease from occurring. It is designed to prevent disease from spreading or recurring.
Tested on Humans
The vaccine is being administered to test its effects on immune response in people between the ages of 18 and 60 with advanced malignant melanoma.
Vaccines based on viruses, by comparison, impart immunity to disease by stimulating white blood cells known as lymphocytes, which in turn trigger the production of antibodies. Antibodies are specific to certain foreign substances and act to remove such matter from the body’s circulation by rendering it incapable of infection.
“It’s not clear what role antibodies play in all of this,†Mitchell said. “We’re still studying that aspect.â€
Preliminary results of the vaccine’s first-phase study, however, resulted in complete remissions for five of 17 patients. Three others experienced partial remissions with greater than 50% tumor shrinkage for more than four weeks, Mitchell said.
Melanomas develop in the skin, mucous membranes, eye and central nervous system--wherever pigment cells are found--and all have varying affinities for tissue invasion and tendencies toward spreading to other sites in the body.
The disease most often affects people with fair complexions, especially those living in tropical or sub-equatorial climates such as Australia, where the disease is reported to occur with high frequency, Mitchell said.
Although malignant melanoma can be exacerbated by excessive exposure to radiant energy, it is not always related to overexposure to the sun because the cancer has been detected deep within the tissue of the eye and in areas of the body normally covered by clothing and inaccessible to sunlight.
Mitchell said studies also show that malignant melanoma is far less common than basal and squamous cell carcinomas, two types of skin cancer that are directly related to overexposure to the sun and that are usually more localized and less serious than malignant melanoma.
Half a Million Cases
The National Cancer Institute estimates that 500,000 people in the United States will develop skin cancer this year and that 7,800 will die of the disorders. About 5,800 of those deaths will be attributed to malignant melanoma, the projections show.
In some of those who have taken the new drug so far, Mitchell said, the remissions were both rapid and dramatic, with cancerous skin and lung nodules shrinking or vanishing within two months after initiation of therapy.
The vaccine is administered along with a booster drug that enhances the production of immune system components that help the body fight disease. The vaccine itself stimulates production of immuno-specific T-cells that develop under the influence of the thymus gland, hence the designation T-cells.
T-cells initiated by the vaccine serve as the body’s key soldiers in fighting the progression of malignant melanoma cells.
“We haven’t been aiming for therapeutic effects to cure them. We’ve just wanted to know what the immunological effects are and to see how it (the drug) affects the immune system,†Mitchell said.
“Phase I was undertaken very gingerly. In Phase II we want to test the dose rate and choose the dose that seems to be most effective.â€
Not New Territory
Although Mitchell’s work marks an advance in a possible new treatment for a malignancy that claims the lives of several thousand Americans annually, it does not break new scientific ground.
Scientists at UCLA, for example, have been trying for several years to produce a similar substance for malignant melanoma, but with only limited results. Researchers elsewhere in the country also have been busily attempting to coax immunizing factors from other types of cancer cells, many with noted success.
Mitchell’s work is related to the body of research that in recent years has produced such substances as interferon, lymphokine-activated killer cells and the interleukin drugs that all activate the immune system.
Just how Mitchell’s substance and others like it will eventually affect cancer therapy hinges to some degree on how much more scientists are able to learn about the elaborate workings of the immune system.
Such research is aimed at producing substances that can be used to fight cancer in tandem with the more conventional approaches, such as radiation and surgery.
Mitchell and his group have been taking biopsied tumor fragments from a number of melanoma patients and mixing the cells to develop the vaccine. The cells are then centrifuged--spun at a high rate of speed--to kill them and break them apart.
Inherent in the cells are elusive chemical factors, as yet unidentified by Mitchell and his team, that have properties capable of prompting the body to create an immune response against malignant cells.
“We know they’re in there,†Mitchell said of the factors. “We just have to know which mixture of tumors is causing the response.â€
Hoover Relation
At Massachusetts General Hospital in Boston, Dr. Herbert C. Hoover Jr. (a distant relative of the nation’s 31st President) said similar experiments have produced a prototype vaccine for colon cancer.
Unlike the melanoma vaccine, Hoover’s treatment for colon cancer, tested in a limited number of patients, is administered after surgery when all signs of the cancer have been removed.
Colon cancer ranks second to lung cancer in the number of malignancies diagnosed annually in the United States. The American Cancer Society estimates that 143,000 new colon cancer cases will be diagnosed in 1987 and that 60,000 people will die of the disease.
“We’re encouraged by the preliminary results, but it’s a very labor-intensive procedure,†Hoover said of the vaccine’s production. He and his team make the experimental drug according to the makeup of a patient’s own tumor cells, which are cultured and prepared prior to surgery.
“This is known as an autologous-style vaccine,†he said. “Eventually we hope to genetically engineer a vaccine that will be similar so that we won’t have to make it from each individual patient.
“If we can get something like that to work, we could have centers all over the country making this vaccine. But a genetically engineered vaccine for colon cancer is still in the stage of a dream,†he said.
Back in the seventh-floor laboratory of the Norris Cancer Center, where long tables are lined with racks of test tubes filled with pink melanoma tissue culture, researchers ponder the potential of their development.
“Within the next couple of years there will be a lot of coordinated research in this area. I can see this happening for all types of cancer,†Mitchell said, referring to vaccine treatments for cancers of the breast, kidney, stomach and bone. “I think there are several diseases where a vaccine approach should be very effective.â€
