Using Cancer to Fight Cancer

By Anastasia Toufexis

For people facing terminal cancer, word of a possible new treatment is a beacon of hope. Few scientists have scattered more rays than Dr. Steven Rosenberg, who has conducted a series of tantalizing though as yet inconclusive experiments at the National Cancer Institute. Rosenberg, a surgeon by training, has repeatedly tried to find new ways to rally the immune systems of cancer patients to combat their own disease. Last week he revealed his most radical effort to date: vaccinating injected patients with their own genetically altered tumor cells in what Rosenberg calls an attempt "to immunize the patient against his own cancer."

Widely covered by the press, the procedure prompted dozens of phone calls to the NCI from patients desperately seeking a cure. Rosenberg stresses, however, that his work is highly experimental. The treatment puts a new twist on classic vaccine strategy. "When you think of a vaccine, it's usually to prevent a disease," he explains. "Here we're actually treating an advanced cancer."

The first two patients -- a 46-year-old man and a 30-year-old woman -- both have terminal-stage melanoma, a form of skin cancer. A few months ago, doctors extracted tumor cells from the patients and inserted into the cells the gene that promotes the production of an antitumor hormone called tumor necrosis ^ factor (TNF). The genetically altered cells were grown in a lab and then injected last week into the thigh of each patient. The hope is that the TNF- primed cells will boost the body's immune system into more vigorous attack against the malignancy.

In a second stage of the treatment, two weeks from now, doctors plan to remove white blood cells from the injection sites and nearby lymph nodes, grow them in a lab and transfuse them into the patients. Studies suggest that such cells will have developed a strong antitumor activity.

Rosenberg and his team have permission from the National Institutes of Health and the Food and Drug Administration to treat 15 people with TNF-gene- altered cells, including patients with advanced kidney or colon cancer. Another 15 individuals with the same diseases may receive injections of tumor cells that have been genetically altered to produce interleukin-2 -- a protein that stimulates tumor-fighting lymphocytes -- instead of TNF. All the patients have failed to respond to standard therapy.

As promising as the approach sounds, some researchers are disturbed by Rosenberg's announcement. They argue that a human trial is premature, given the limited results of this treatment in animals. While Rosenberg's method has been shown to prevent the formation of new tumors in healthy mice, there is no published evidence that it can counteract existing cancers. Rosenberg, however, maintains that he has ongoing animal experiments to support his work and that he submitted extensive unpublished research data before obtaining permission to proceed: "This was reviewed for eight months by about 50 scientists on at least five committees at the NIH and FDA."

Rosenberg has also been criticized for inflating patients' hopes by publicizing his experiment before there are any results to report. "It's a very high-profile research activity that Steve Rosenberg is running," Dr. Philip Leder of Harvard University School of Medicine told the New York Times. "He didn't come to you after the experiment was successful. He came at the beginning, because it might be quite uninteresting when it's all finished." Given all the attention and elevated hopes, Rosenberg should reveal his results -- even if they are uninteresting -- with the same alacrity he shows in announcing the start of an experiment.