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9/19/2002

Immunotherapy Can Suppress Metastatic Cancer

Cheryl A. Thompson

By replacing nearly all of the immune system with cells known to attack a tumor, scientists at the National Institutes of Health have shown that immunotherapy can repel aggressive metastatic cancer.

Steven A. Rosenberg, who led the project, said this is the first time that an ineffective immune system has been replaced with an effective one capable of destroying disease, in this case metastatic melanoma. A description of the study was published online today in Science Express.

Thirteen adults with metastatic melanoma unresponsive to standard therapies underwent the "highly experimental treatment," Rosenberg said.

For each patient, a biopsy of the melanoma was examined in the laboratory. The tumor-infiltrating lymphocytes were isolated and compared for their propensity to attack the patient's tumor. Large populations of T cells were then grown from the most active tumor-infiltrating lymphocytes.

But previous studies with highly reactive T cells had shown that the transferred lymphocytes failed to persist in patients' immune system. To overcome that obstacle, Rosenberg said, his team wiped out nearly all of the original immune system by administering cyclophosphamide and fludarabine. Seven days later, with about 10 percent of the original immune system remaining, the patients received "staggeringly high numbers" of the tumor-specific T cells, upward of 20 billion, in 20 minutes through a peripheral vein and then five to 12 doses of interleukin-2, he said.

At least half of the tumors shrank in six patients, a response that has lasted more than 24 months for the youngest patient, an 18-year-old man who had had a volleyball-sized mass in his pelvis when he underwent the new therapy, Rosenberg said. Four other patients had a mixed response, with substantial shrinkage of at least one metastatic deposit. Three patients did not respond at all, a result that puzzles Rosenberg.

Although all of the patients survived the treatment, such a major adjustment of the immune system did cause problems. A lymphoproliferative disorder related to Epstein-Barr virus developed in one patient who was initially seronegative for the virus, and a noninvasive pneumonia developed in another patient. Autoimmunity developed in five patients: depigmentation of the skin occurred in four, and an inflammation of the pigmented part of the eye developed in another patient.

Rosenberg said that immunotherapy, such as the treatment his group tested, might become the fourth type of cancer therapy. Surgery, radiation, and chemotherapy cure about half of cancer patients, he said, but these options use "external forces" to fight disease. Immunotherapy, on the other hand, magnifies a patient's own defense against cancer.

Rosenberg discussed his research results at the 21st Annual Science Reporters Conference in Washington, D.C. The conference is organized by the American Medical Association.