- The Washington Times - Friday, September 1, 2006

Researchers at the National Cancer Institute have performed the first successful use of gene therapy as a cancer treatment, in a study of 17 patients with advanced melanoma, a deadly form of skin cancer that kills almost 8,000 Americans annually.

The scientists genetically altered the white blood cells of the patients, converting their normal immune cells into cancer-fighters. Two patients have remained disease-free for at least 18 months, the federal investigators reported yesterday in a study in the online version of the journal Science.

“These results represent the first time gene therapy has been used successfully to treat cancer. Moreover, we hope it will be applicable not only to melanoma, but also for a broad range of common cancers, such as breast and lung cancer,” said Dr. Elias A. Zerhouni, director of the National Institutes of Health, of which NCI is a part.

Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society, called the study, which he had seen but was not involved with, “important and exciting, since it shows you can effectively use gene therapy to treat cancer.”

“This is the first demonstration in people that this concept works, and it is the result of many decades of research efforts. The investigators found no significant side effects from the treatment,” which has not always been the case in trials involving gene therapy, Dr. Lichtenfeld said yesterday.

The NCI researchers who conducted the study, led by Dr. Steven Rosenberg, already knew that autologous lymphocytes — or a person’s own white blood cells — can be used to treat melanoma that has spread throughout the body. But only some people have that specialized type of white blood cell in their body naturally.

Dr. Rosenberg, long a leader in cutting-edge cancer research at NCI and President Reagan’s surgeon for his 1985 operation for colon cancer, strove to find a way to transform white blood cells into those specialized anti-cancer blood cells, which recognize tumors as abnormal cells and fight them.

Dr. Rosenberg and his team drew a small blood sample containing normal lymphocytes from melanoma patients who had failed previous therapy, and then infected those cells with a retrovirus, another type of cell that, like a cancer, attaches itself to normal human cells though a specific protein called T-cell receptors.

Like a vaccine introduced into the body to “teach” it how to fight off a disease, the white blood cells then “learn” to destroy the melanoma cells through their similarity to retroviruses. The anti-cancer cells are then multiplied in the laboratory and reintroduced into the patient.

“This approach takes advantage of markings on the surface of cells that distinguish cancer cells from normal cells,” Dr. Lichtenfeld said. “They insert a genetic code into the lymphocytes to find cancer cells and destroy them.”

The process did not slow down the cancer in the first three patients in the NCI experiment.

“The [cancer-fighting] lymphocytes in those patients did not last long enough to work,” Dr. Lichtenfeld said. So the researchers modified the treatment for the remaining patients in the study, making sure the anti-cancer cells were put into the patients in their most active growth phase.

After one month of gene therapy, the cancer-fighting white blood cells remained in the patients’ bodies, in strengths ranging from 9 percent to 56 percent of the initial infusion. No toxic side effects attributed to the genetically modified cells were reported in any patient.

The two male patients who have been free of cancer for a year and a half, ages 52 and 30, experienced both cancer regression and sustained high levels of the genetically altered cells in their systems. When gene therapy began, their cancers already had spread, respectively, to their liver and lungs. But those problems are gone at this time.

“Getting a complete response like this in patients in their circumstances — having liver and lung disease — is unusual, as is the fact that they have had no evidence of disease for so long,” Dr. Lichtenfeld said.

The researchers are working to improve their 13 percent success rate. Toward that end, they are seeking to engineer more-powerful white blood cells through such means as developing cells that bind to tumor cells more tightly and by inserting molecules that can assist in directing the cells to cancerous tissues.

“We have now [developed] other lymphocyte receptors that recognize breast, lung and other cancers,” Dr. Rosenberg said.

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