After a lengthy review that proved far more rigorous than researchers had expected, the Food and Drug Administration approved a highly experimental treatment for advanced cancer yesterday.
The decision swept away the final obstacle to the radical new therapy, an attempt to treat patients by infusing them with genetically engineered blood cells custom-designed to target and destroy tumors.
The cells will harbor the gene for tumor necrosis factor, a potent enzyme that in animal tests has been shown to dissolve bulging tumors within hours after application.
The National Institutes of Health and its acting director, Dr. William Raub, approved the therapy last summer.
With the last regulatory hurdle cleared, Dr. Steven A. Rosenberg of the National Cancer Institute in Bethesda, the researcher in charge of the project, plans to begin testing the therapy on three cancer patients in four to six weeks. "I'm chomping at the bit to get started on this," he said.
The patients are among 8,000 to 10,000 Americans who suffer from metastatic melanoma, a deadly skin malignancy that has spread throughout their bodies. They are not expected to live beyond two or three months.
One reason metastatic melanoma has been chosen as the candidate tumor for the experimental approach is that it resists virtually all conventional forms of cancer treatment, such as chemotherapy or radiation.
And with rates of melanoma rising by 4 percent to 5 percent a year in the United States, cancer specialists say they are desperate for creative battle plans such as the gene therapy method.
"This is an exciting approach that is totally different than any used before," said Dr. Darrell S. Rigel, a dermatologist and melanoma specialist at New York University Medical Center in Manhattan.
"As a practicing physician who deals with advanced melanoma, it's been so frustrating to us that there is no effective treatment for it. This one has a chance of working."
Dr. Rosenberg and other researchers say that, in theory, gene therapy could prove effective against many different types of advanced cancer that have spread beyond the reach of a surgeon's blade.
But cancer specialists caution that even if the therapy works -- and that is a big if -- it would take years before the experimental method was commonly available.
"We're already getting 20 or 30 calls a day asking about this work," Dr. Rosenberg said. "But we've only gotten approval to try it on 50 patients, and we can only handle one or two a week."
Scientists have known for several years that tumor necrosis factor, a compound naturally produced by the body to fight bacterial infections and to help modulate the immune system, can also destroy tumors when injected into rodents in high doses.
But initial attempts to treat cancer patients with simple injections of the purified factor failed. Researchers found that inoculations of the compound strong enough to dissolve the cancer dangerously lowered blood pressure and came close to killing the patients.
Dr. Rosenberg reasoned that if extremely high doses of tumor necrosis factor could be delivered to the tumor sites, but to nowhere else in the body, the treatment might be both safe and effective.
To ferry the compound to the cancer cells alone, he and his colleagues will package the gene for tumor necrosis factor in tumor-infiltrating lymphocytes, white blood cells that have been shown to home in on tumors. Those blood cells will be isolated from cancer patients and grown in large quantities in the laboratory, a procedure that takes about four weeks. Using a genetically engineered virus, the Rosenberg team will insert the necrosis factor gene into the lymphocytes and then re-infuse the manipulated cells into the patients.
If the experiment works as conceived, the lymphocytes will ferret out even tiny pockets of malignant cells in the body, latch onto their surfaces and douse them with the powerful anti-tumor compound produced by the gene, while sparing the rest of the body from any biochemical onslaught.
Dr. Rosenberg predicts that if the procedure succeeds, the malignancies should begin to shrink within weeks of the first cell infusion.
Lymphocytes not able to home in on tumors are rapidly flushed from the body, he says, suggesting that the potential harm from circulating tumor necrosis factor is slight.