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Scientists Hail Cancer Study

A gene therapy method used to cure melanoma with patients' immune cells needs work. But it promises a new way of fighting tumors.

September 01, 2006|Karen Kaplan | Times Staff Writer

Scientists for the first time have genetically modified tumor-fighting immune cells, allowing patients to rid themselves of an aggressive form of cancer, according to a study released Thursday.

The technique, used to cure two patients with advanced melanoma, paves the way for a new approach to fighting cancer by harnessing -- and boosting -- the body's own immune system instead of relying on toxic chemotherapy and radiation treatments to kill out-of-control tumors.

The researchers from the National Cancer Institute, whose findings were published online by the journal Science, say the strategy could be adapted to treat breast, prostate, lung, colorectal and other common cancers.

"It's obviously very exciting," said Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, who was not involved in the research. "It's a proof of concept of being able to develop a technique where they can use a patient's own blood cells to fight cancer."

Dr. Steven A. Rosenberg, chief of the National Cancer Institute's surgery branch and senior author of the study, said the results reaffirm the promise of gene therapy after several high-profile setbacks.

Rosenberg and others cautioned that it would take several years to translate this initial success into a practical therapy.

They added that there is still more failure than success with the technique. Fifteen other melanoma patients enrolled in the study failed to show sustained improvement from the modified immune cells. Twelve of those patients have died, and the other three are near death, Rosenberg said.

But the success with two patients, who are cancer-free more than a year and a half after their treatment, was enough to demonstrate the possibility of a new front in the war against cancer.

"The important thing is this approach worked," said Dr. Margaret Kemeny, director of the Queens Cancer Center of Queens Hospital in New York. "Can they make this approach work more often? That is the question."

Melanoma accounts for only 4% of skin cancer cases, but it is the most lethal type. More than 62,000 patients will be diagnosed with melanoma this year, and 7,910 people will die from it, according to estimates from the American Cancer Society.

Rosenberg had previously discovered that some melanoma patients are able to generate a type of immune cell, called a T cell, that recognizes the tumor cells as unwanted intruders and attacks them.

T cells work by attaching to antigens, distinctive proteins that reside on the surface of tumor cells. Once they lock on, the T cells secrete tumor-destroying hormones. Melanoma cells are coated with an antigen called MART-1.

In an earlier experiment, Rosenberg's team removed white blood cells from patients with metastatic melanoma and isolated the most aggressive tumor-fighting T cells. Those cells were multiplied in the lab and reinjected into patients after their immune systems were cleared using chemotherapy drugs.

The experiments showed promise, but about half the patients didn't have any T cells that were able to target melanoma, Rosenberg said. So he decided to give ordinary T cells the genes they would need to recognize MART-1.

The researchers spliced the genes for making the anti-MART-1 receptor into a disabled retrovirus. Then the retrovirus was let loose on a few million white blood cells that had been removed from each melanoma patient.

As the virus infected the cells, the new gene was transferred into the T cells. When the cells multiplied, the subsequent generations also had the anti-MART-1 receptor, Rosenberg said.

The team used chemotherapy to wipe out the patients' existing immune cells, then replaced them with the genetically modified cells.

Some patients showed hardly any uptake of the new genes, but half the patients wound up with the new gene in at least 20% of their T cells.

After three months, eight patients still had detectable levels of the genetically modified T cells in their systems.

In one patient, the engineered T cells grew to make up about two-thirds of his immune system. Though previous treatments with powerful drugs and surgery had failed to stem his cancer, the gene therapy shrank an enlarging tumor on his lung until it disappeared altogether.

Another patient, 53-year-old Mark Origer, had tried drugs, surgery and an experimental vaccine before enrolling in the gene therapy trial. By the time he had his first checkup about a month after getting the souped-up T cells, his tumors had shrunk in half.

"It was euphoric," said Origer, who was diagnosed with melanoma in 1999. "I had waited so many years to find something that was working."

The T cells eradicated the tumor under his arm and shriveled another tumor in his liver by 89%. He has been cancer-free since the remaining mass was surgically removed in October.

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