In the first use of foreign genes in the cells of humans, specially groomed cancer-fighter cells carrying a new "marker" gene were shown to have kept on trying to kill cancer cells two months after they were injected into the patient.
The experiment was not gene therapy, although it is widely regarded as a first step in that direction. The new gene was added simply as a marker to track the fate of the patients' natural cancer-fighting cells, which had been removed, grown in large quantities in the laboratory, and reinjected as an experimental therapy. In true gene therapy, the new gene would confer some therapeutic power on the cells.
In a report in today's New England Journal of Medicine, National Institutes of Health researchers describe what happened to the cells in the first few patients who underwent the marker-gene procedure.
"It is the first step in the dawn of a new era of treatment in medicine," said Stephen A. Rosenberg, chief of surgery at the National Cancer Institute and head of the research group that included W. French Anderson of the National Heart, Lung and Blood Institute and NCI's R. Michael Blaese. "It has been a long time in coming."
Of the five patients reported on in the paper -- all of whom had melanoma skin cancer that failed to respond to conventional therapy -- two had a full or partial remission and two died from the progression of the disease. Three more patients have since been treated, for a total of eight receiving gene-altered cells.
The experiment showed that "you can use this technology to introduce genes into human cells safely," said Rosenberg, who has been mass-producing the cancer-fighting cells for several years. "There were no dangers to the patients, the health care personnel or the public."
The technology uses specially engineered viruses to carry genes into human cells. Into the viruses the NIH researchers first installed a bacterial gene to act as the marker. When the cancer-fighting white blood cells, called tumor-infiltrating lymphocytes, were removed from the patients to be grown in the laboratory, the viruses were allowed to infect them, splicing their genes into those of the cells.
Rosenberg's treatment works dramatically in about 10 percent of melanoma patients and slows the disease in about half, but fails to help the rest.
Gene therapy is poised to take the next step. On Monday, Rosenberg asked the Food and Drug Administration for permission to load the white blood cells with genes intended to make them more potent cancer fighters. The NIH team already has received permission from several scientific review committees to proceed with what amounts to true gene therapy.
The FDA has 30 days to make a decision. "I am hoping for approval in the next one to two months," he said. "We are ready to go. We will start within days of approval."