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Attack of the Clones: Immune cells single out melanoma tumors

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10:32am, November 13, 2002
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Because cancer arises from a person's own cells, it's often overlooked by the immune system. In the past decade, however, scientists have discovered that some immune system cells do indeed recognize tumor cells. There's still a problem: Being few in number, these cells are typically ineffective in fighting cancer.

Scientists can extract these potential fighters from cancer patients. Then they culture the rare cells, which are a type of T cell, to greatly expand their number. Two new studies indicate that when these multiple copies, or clones, of T cells are injected into the patients, they sometimes put the brakes on cancer.

One team of scientists treated 13 patients who had melanoma that had spread, or metastasized, to lymph nodes or internal organs. For each patient, the researchers made billions of copies of the individual's T cells that target a specific protein on melanoma cells, says Steven A. Rosenberg, chief of surgery at the National Cancer Institute in Bethesda, Md.

He and his colleagues gave the patients drugs that kill off their white blood cells, including T cells, before injecting them with the cloned T cell hoard.

The team also provided the patients with interleukin-2, a compound that induces T cell growth. The injected T cell clones soon dominated the participants' immune system, even after the other cells rebounded from the drugs' effects, Rosenberg notes.

The treatment beat back the cancer in six of the patients for periods ranging from 2 to 24 months. In each of four other patients, some tumors grew and others shrank, the team reports in the Oct. 25 Science.

One 18-year-old patient's cancer, which had spread to lymph nodes in his pelvis and elsewhere, has been in remission for 24 months since treatment.

"This is as close to a miracle as I've seen as a clinician," Rosenberg says.

In the other study, Seattle scientists similarly extracted and multiplied T cells from 10 patients fighting advanced melanoma.

These patients didn't get drugs to kill their white blood cells and received less interleukin-2 than Rosenberg's patients did, says Cassian Yee, an immunologist at the Fred Hutchinson Cancer Research Center in Seattle. After the treatment, Yee's patients had a much lower ratio of T cell clones to total T cells than patients in the other study did.

The Seattle patients also showed less dramatic results. Cancer stabilized in half of them for periods ranging from 3 to 21 months, but none of these patients showed actual cancer regression, Yee and his colleagues report in an upcoming issue of the Proceedings of the National Academy of Sciences.

Yee's patients, however, showed fewer side effects than Rosenberg's patients did.

In the upcoming Proceedings, molecular biologist Drew Pardoll of the Johns Hopkins University Medical Institutions in Baltimore says that these two studies indicate that T cells revved up with interleukin-2 "are indeed capable of trafficking into even large metastatic tumor deposits and eliminating tumor cells."

"This is a novel approach that takes advantage of T cells' inherent ability to undergo proliferation," says Charles D. Surh, an immunologist at the Scripps Research Institute in La Jolla, Calif. He suggests that in future experiments, researchers expand populations of T cells targeted toward several proteins found on tumor cells rather than toward just one protein.

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