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New approach to immunotherapy shows promise against advanced melanoma

Adoptive transfer, a new technique in which large numbers of a patient's T cells--- activated to attack the patient's individual tumor--- has shown great promise against advanced melanoma, according to an article in the September 19th online publication of Science.

Researchers at the National Cancer Institute exposed T cells to tumor samples, stimulated cell division, and then transfused a large number of T cells back into the patient after chemotherapy had depleted the supply of inactive cells.

In the study, 13 patients with metastatic melanoma that had not responded to standard treatments were treated with immune cells produced specifically to destroy their tumors. The treatment resulted in at least 50 percent tumor shrinkage in six of the patients, with no growth of tumors or appearance of new tumors. Four additional patients had some cancer growths disappear.

Researchers have tried previously to treat cancer with immune cells but the cells did not survive well in the body. "In the past, only a fraction of a percent of the cells we injected were able to survive, and they would persist for only a few days," said Steven A. Rosenberg, M.D., Ph.D., of the National Cancer Institute, a researcher on the study.

Improvements in the way immune cells are generated in the laboratory and the way patients' bodies are prepared to receive them, however, have led to dramatically different results. "We have been able to generate a very large number of immune cells that appear in the blood and constitute a majority of the immune system of the patient. These persist for over four months and are able to attack the tumor," Rosenberg said.

With the adoptive transfer technique, researchers used a small fragment of each patient's melanoma tumor to activate some of the patient's T cells. After the cells had multiplied to a sufficient number, they were administered to the patient. Each patient was also given a high dose of interleukin-2 to stimulate continued T-cell division in the body. Prior to the infusion, chemotherapy was used to deplete the patients' inactive immune cells and provide an opportunity for the new T cells to repopulate the immune system.

Analysis of blood and tumor samples from many of the patients who responded favorably to the treatment revealed that the administered immune cells were thriving, multiplying rapidly, and attacking tumor tissue. T cells activated against melanoma became the major component in these patients' immune systems. They persisted for several months and were able to destroy metastases throughout the body.

Over time, patients' endogenous immune systems recovered, restoring full ability to fight infections. Researchers report that among the patients in the study, only occasional opportunistic infections developed during immunotherapy. Other side effects were mild autoimmune disorders. Autoimmune effects were mild and easily controlled.

Although the treatment is highly experimental, researchers are optimistic that it may, in the future, be useful for many tumor types. Similarly, the same technique could potentially be used to treat some infectious diseases such as AIDS.







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