An experimental vaccine has worked well enough in 11 patients with lethal skin cancer for researchers to expand its use to more patients and to other types of cancers.

The vaccine destroyed a minimum of 80 percent of tumors in 11 people suffering with advanced-stage melanoma, in which the cancer had spread throughout their bodies. The treatment did not cause the wrenching side effects so common with cancer drugs and radiation.

"The fact that we got that kind of tumor destruction in a substantial number of patients with the last stages of the disease was quite exciting and very unexpected," says Glenn Dranoff, assistant professor of medicine at Harvard Medical School. Dranoff is leader of a group of researchers at five Harvard-affiliated hospitals in Boston.

The vaccine they developed does not prevent cancer, rather it stimulates a person's immune system to recognize tumors and attack them. Recently a newer version of the vaccine has been developed that is easier to make. Researchers also have begun a program to test the vaccine on lung cancer, which kills more people than all other cancers combined.

Studies in animals show that the same type of vaccine kills the mouse equivalent of ovarian, leukemic, and brain tumors. "This year, we will test the vaccine in the same type of human cancers," Dranoff promises.

Patients Live Longer

In the first vaccine tested, Dranoff's group injected it into 21 patients expected to die of melanoma. No other treatment was available to save them.

Life expectancy for those in the most advanced stages of the disease runs eight to nine months. Most of those who got the vaccine lived longer than nine months. Five still survive; two of them remain alive after more than three years. However, the researchers won't take credit for their survival.

"We can't prove what, if anything, the vaccine did for these people," Dranoff says. "They might have lived that long without the treatment."

The 21 patients had pieces of their tumors removed in order to make individualized vaccines. After receiving as many as 24 injections of the vaccine, 16 agreed to additional surgery to provide post-vaccine tumor samples. That's how the investigators determined that most tumor cells in 11 of the patients had been killed.

Pictures of cells taken through a microscope before vaccination show fat, round cancer cells. In those taken afterward, you can see how the body's immune cells "ate" the malignant cells and even destroyed blood vessels that supplied them with nourishment.

"But we didn't kill them all," Dranoff admits. "Patients who remained alive longest had less amount of tumor than those who did not live as long, even though all were in the most advanced stage. What we want to do is try the treatment on people in an earlier stage of the disease."

Researchers shipped surgically removed pieces of the tumors of the first 21 patients to a biotechnology firm in California. Here they were grown and engineered to make a hormone known as GM-CSF (granulocyte-macrophage colony-stimulating factor), which stimulates the immune system to recognize and attack cancer cells. Genes to produce the hormone were put into viruses, which in turn were put into the tumor cells.

The researchers then irradiated the engineered cells so they couldn't grow and produce new tumors. The cells were shipped in ice back to Boston, then thoroughly tested for safety before being injected into the patients.

"The actual injection of the vaccine was anticlimactic," recalls Dranoff. "It took no longer than a flu shot, and the only reaction was some redness, swelling, and itching."

The vaccine took eight to ten weeks to prepare, much too long for people expected to live only eight to nine months. The newer vaccine, in contrast, can be prepared in a single day. And it is carried by a more benign virus, one less likely to cause problems, thus eliminating the need for much testing.

Dranoff and co-researcher Robert Soiffer performed their research at the Connell-O'Reilly Laboratory, a special facility for doing human gene therapy at the Dana-Farber Cancer Institute. Other key members of their team include Thomas Lynch and Martin Mihm of Massachusetts General Hospital, and Richard Mulligan of Children's Hospital.

Preventing Cancer?

"We're currently evaluating the more easily made vaccine in other melanoma patients," Dranoff says. "We want to determine if we get the same kind of tumor reduction. I'm optimistic that we can."

Because the vaccine does not kill all the tumor cells, the team intends to explore the possibility of repetitive inoculations, using additional vaccines made from tumor cells that didn't respond the first time. Finally, they want to give the vaccine earlier in the course of the disease when the tumor burden is less.

"It will take several years before we will be able to test the efficacy of the vaccine in several hundred patients," Dranoff notes. Time is a big factor here because melanoma is the fastest growing cancer in the United States. New cases are expected to rise from 32,000 in 1994 to an estimated 41,600 this year, and deaths from 6,900 to 7,300 during the same period.

Dranoff and his colleagues will try the same approach to treat lung and other cancers. Meanwhile, dozens of other research groups, both at Harvard and around the world, are working on other types of cancer vaccines.

Will there ever be a vaccine that prevents cancer? "It's not unreasonable to speculate that there will," Dranoff answers cautiously.

He cites efforts in China that appear to be decreasing the incidence of liver cancer. The major cause of cancer deaths in that country, it was linked to the hepatitis B virus some 20 years ago. Mass immunization programs, begun 10-15 years ago, now show a clear reduction in hepatitis, and there are initial indications that liver cancer is declining.

Although most big cancer killers in the United States, like lung, colon, breast, and prostate cancers, are not related to viruses, "China provides proof of the prevention principle," Dranoff says. "At this point, it's not fantasy and it's not reality; it's just optimistic thinking."