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New Method of Gene Therapy for Treating Advanced Melanoma

Melanoma accounts for only about 4% of skin cancer cases, but it’s the most serious and aggressive type of skin cancer. An estimated 62,190 new cases will be diagnosed in the U.S. this year and approximately 7,910 people will die of the disease. A team of researchers at NIH’s National Cancer Institute (NCI) have now genetically engineered patients’ own white blood cells to recognize and attack advanced melanomas. This is the first time that gene therapy has been used successfully to treat cancer.

Researchers have previously shown that lymphocytes — white blood cells from the immune system — can be used to treat melanoma. Lymphocytes are removed from patients with advanced melanoma and the most aggressive tumor-killing cells isolated and multiplied in the lab. These are then reintroduced into patients who’ve had their remaining lymphocytes depleted. However, this method only works for people whose lymphocytes already recognize tumors as abnormal and it’s not effective for other cancers.

NCI researchers led by Dr. Steven A. Rosenberg sought an effective way to convert normal lymphocytes into cancer-fighting cells. They drew a small sample of blood that contained normal lymphocytes and infected the cells with a retrovirus in the laboratory. This retrovirus delivers genes encoding proteins called T cell receptors (TCRs). When the genes are turned on, they cause the lymphocytes to make TCRs, which then decorate their outer surfaces. The TCRs act as homing devices for the cells, recognizing and binding certain molecules found on the surface of tumors. The lymphocytes then destroy the cancer cells they’re attached to.

In the online edition of the journal Science on August 31, 2006, the researchers describe how these engineered lymphocytes were infused into 17 patients with advanced metastatic melanoma that had not responded to previous treatments. The first group of three patients showed no delay in the progression of their disease. The researchers then returned to the lab to improve the treatment of lymphocytes so that they could be administered in their most active growth phase.

All the patients who received the improved treatments still had at least 10% of their lymphocytes making TCR for more than two months. Two of the patients experienced cancer regression and remained disease-free over a year and a half after treatment. There were no toxic side effects attributed to the genetically modified cells.

Now that the researchers have proved this strategy can be successful, they're testing several methods to improve its effectiveness. In addition, Rosenberg said, “We have now expressed other lymphocyte receptors that recognize breast, lung and other cancers.”

“These results represent the first time gene therapy has been used successfully to treat cancer,” ��ѿ��ý Dr. Elias A. Zerhouni said. “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.”