New Weapon in the Cancer War?

By Joe Levine

That the patients were only laboratory mice did not detract from the results: 100% cured of colon cancer that had spread to the liver, 50% cured of colon cancer spread to the lungs. These are remarkable cure rates for malignancies that are virtual death sentences for both mice and people. The encouraging results were announced last week by a researcher of near celebrity status, Dr. Steven Rosenberg of the National Cancer Institute. It was Rosenberg who, as spokesman for the team of doctors performing colon surgery on Ronald Reagan, shocked the nation last year by announcing on television, "The President has cancer." And it was Rosenberg who caused a flurry in December with the report that he had used a natural body chemical to stimulate cells from the immune system to destroy human tumors. Now the NCI researcher and his colleagues were announcing a new cancer-killing cell in the body that was "50 to 100 times" as effective in animal trials as the one they experimented with last year.

As he has done in the past, Rosenberg went out of his way to avoid raising any false hopes of a quick cancer cure for humans. "This has all been done with mice," he stressed. "There are things that work in mice that do not work in people." Still, some of the results published last week in the journal Science were compelling. For example, mice subjected to the new treatment proved to be immune to malignancies seeded by cells from the original tumor. And the NCI team has already isolated the same kind of powerful cancer-fighting cell in humans. "It's potentially very exciting," Rosenberg concedes. He believes the U.S. Food and Drug Administration will agree and approve the treatment for human trials within the next two months.

The new treatment is a form of immunotherapy, an experimental technique that has been refined substantially in the past five years as an alternative to surgery, radiation or chemotherapy. Immunotherapy enhances the immune system's disease-fighting capabilities by using some of the body's own chemical agents -- the interferons, tumor-necrosis factor or interleukins, for example. Last year, in one of immunotherapy's most promising clinical trials to date, Rosenberg's team used the hormone-like substance interleukin-2 to turn certain white blood cells into cancer destroyers called lymphokine- activated killers. Reinjected into the bloodstream with more IL-2, LAK cells shrank or eliminated tumors in several patients. As news of the experiment spread, desperate cancer victims around the country besieged the NCI for LAK treatment. Able to take only a handful of patients, the institute is still turning away hundreds each week. Nearly overlooked in the news reports was Rosenberg's warning of IL-2's side effects, which include internal bleeding and retention of fluid in the tissues. Indeed, the large doses of the substance required to supplement the LAK cells caused at least one test subject to die of lung failure. LAK cells, it turned out, are primitive weapons, difficult to direct at a single target. They are like a "rocket that just goes off," says Dr. Ellis Reinherz, of Boston's Dana-Farber Cancer Institute, as opposed to "one with a guidance system." Scientists had long known of cells in the body with such guidance systems but assumed the cells to be either too few in number or too weak to overcome cancer cells in people who develop malignancies.

The new treatment answers those problems and then some -- at least in mice. Rosenberg's team found potential guided-missile cells called T lymphocytes in tumor tissue removed from the mice. They minced the tumor, added IL-2, and soon a whole colony of the anticancer cells -- called tumor-infiltrating lymphocytes -- were thriving while the cancer cells were dying out. After 15 days, the researchers injected millions of TIL cells back into the mice. The cells, as if by instinct, sought out the tumors that had spread from the original cancer and attacked them. To keep the TIL cells vigorous and growing, the NCI team had to inject the mice with additional IL-2, but only about a tenth as much as in the LAK treatments. As a result, few serious side effects were apparent. With the addition of cyclophosphamide, a drug that Rosenberg believes suppresses immune-system cells that might otherwise impede the TIL cells, the treatment achieved its spectacular success rates. Most important, the combined therapy cured mice of advanced colon cancers that in parallel animal experiments had withstood the LAK cells. Can TIL immunotherapy work in humans? "There are some questions," says Dr. Alexander Fefer, a University of Washington researcher who has pioneered in the development of T cells that target malignancies. Perhaps the most significant question is whether human TIL cells will exhibit the same homing instincts as their counterparts in mice. If so, TIL immunotherapy could be ideal for catching stray cancer cells missed by surgery and destroying them before they can seed other tumors. Also, Fefer wonders, can sufficient numbers of TIL cells be produced to vanquish human tumors? Although only clinical trials will provide the answers, Fefer admits he is "optimistic about this (Rosenberg's) approach or an approach like it."

Other experts seemed equally impressed. After hearing of the NCI report, Allan Hess, a Johns Hopkins University researcher, summed up the mood of cancer specialists. "We're really beginning to understand what goes on in cancer," he said. "Now we're taking that knowledge and applying it."

With reporting by Christine Gorman/New York and Dick Thompson/Washington