Cancer-Killing Cells Zap Melanoma

Flooding the body with laboratory-engineered white blood cells shriveled melanoma tumors in a small group of seriously-ill patients, leaving some virtually free of the disease, according to researchers at the National Institutes of Health.

A team led by Dr. Steven A. Rosenberg of the National Cancer Institute used amplified lymphocytes - the body's white blood cells - to attack melanoma tumors in 13 patients. Ten of those patients are still alive, four are "virtually cancer free" and two others have experienced "substantial" shrinkage of their tumors, Rosenberg said.

Rosenberg, who has spent years developing ways to enlist the body's own immune cells to fight cancer, said his team has learned how to grow huge numbers of cancer-fighting cells within the patient, enough to overwhelm the tumors.

"The major difficulty is to get enough immune cells to react against the cancer," he said. In previous efforts, researchers were able to prompt a small fraction of the immune cells injected into the body to attack the cancer and then only briefly.

"We would end up with a half percent (of the total immune cells) and they are gone two weeks later," he said. "With the current approach, we can get 90 percent of the body's lymphocytes to react against the cancer."

The research, to be published Friday in the electronic version of the journal Science, was described as "an important advance" by others in the field.

"This demonstrates something that has not been shown before in therapy using immune cells," said Dr. Cassian Yee, a researcher who has experimented with a similar technique at the Fred Hutchinson Cancer Research Center in Seattle. "It is important because they showed they could grow significant numbers of T-cells in patients that could recognize tumors. In terms of using T-cells (lymphocytes) to treat melanoma, it is an important advance."

The body makes T-cells that will attack cancer, but the natural number is seldom large enough to check the disease's progression. To amplify these cells, Rosenberg and his group removed cancer-killing T-cells from the patients and then grew the cells until there were billions.

The researchers then made room for the new cells by treating the patients with chemotherapy to suppress the body's natural T-cell count.

After injections of interleukin-2, a protein that stimulates lymphocytes, more than 70 billion of the special T-cells were injected into the patients where the cells multiplied rapidly.

"For the first time we've been able to get the cells that we give to survive and grow inside the body," Rosenberg said. "When it does that, it attacks the cancer and causes the cancer to shrink."

The results were striking and swift, the researcher said.

"A young boy we treated two years ago had two pounds of tumor and he's now disease free," Rosenberg said. He added that cancer is undetectable in two others, while tumors are 99 percent gone in another. For two others, Rosenberg described the results as "substantial regression." Three of the original 13 patients have died, he said.

Rosenberg said the special T-cells persist in the body, with some patients testing at 75 percent to 80 percent levels seven months after therapy.

The lymphocytes combat cancer by attacking antigens on the melanoma tumor cell surface. A normal cell which makes pigmentation in the body has this same antigen. As a result, in some patients the lymphocytes attacked normal cells, causing a type of mild autoimmune disease.

Rosenberg said four patients developed white patches on the skin where the T-cells killed the pigmentation. The color in the eye of one patient was also attacked, causing an inflammation of the iris. The condition is now being controlled with steroid drops, said Rosenberg, "and his vision is normal."

Although the technique has been used only against melanoma, a deadly skin cancer, Rosenberg said it may work against other types of cancer. His group is now preparing to test it against breast, prostate and ovarian tumors.

Rosenberg emphasized that immune cell therapy against cancer is still "highly experimental" and at least two years away from being ready for general cancer patients.

"We're still improving it. We're still trying to understand why it works in some patients and not others," he said. "It is certainly not ready for widespread use, but it is being developed for that purpose."