T cells Take on Tumors

19 September 2002 (All day)

Top gun. A tumor-fighting T cell (center), surrounded by red blood cells, proved to be a vicious attacker of melanoma.

Tumors normally fend off any attacks by the immune system. But now scientists have found a way to give immune cells an edge, thereby shrinking tumors throughout the body. The work breathes life into cancer immunotherapy, a field that has struggled to achieve success in humans.

Unlike foreign intruders such as bacteria, tumor cells are the patient's own and hence are less viciously attacked by the immune system. However, the tumor surfaces of certain cancers have antigens, molecules that awaken the immune system and induce it to respond. Melanoma, a particularly dangerous form of skin cancer, is one of these. But scientists have struggled for years to harness the small number of T cells, the immune system's first line of defense, that are thought to fight these tumors.

To craft a powerful immunotherapy treatment, immunologist Steven Rosenberg and his colleagues at the National Cancer Institute (NCI) in Bethesda, Maryland, obtained tumor samples from 13 patients with metastatic melanoma. Searching for T cells that had infiltrated the tumors, they collected as many as 50 T cell samples from a single tumor; next, the team tested each batch of T cells against other tumor samples from the same patient. This allowed the researchers to handpick the two or three T cell samples that most effectively killed cancer cells.

Reasoning that the selected T cells, to be effective, would have to make up the bulk of cells in each patient's immune system, the team administered chemotherapy to the patients to temporarily wipe out substantial numbers of existing immune cells. Then they reinfused the highly aggressive T cells, which had been allowed to multiply. In six of the 13 patients, all tumors decreased in size by at least 50%. The NCI group saw some tumor shrinkage in four others, they report online in Science 19 September. Ten of the volunteers, all of whom were expected to die within a few months, remain alive 6 to 24 months after the first treatment.

"It's essentially what all of us have been striving for in immunotherapy," says James Mulé, an immunologist at the University of Michigan Medical School in Ann Arbor. Still, "it's hard to predict how this will turn out" in the longer term and in larger groups of patients. And although the treatment reached metastases buried in the lungs and liver, it didn't work well for everyone, and Rosenberg doesn't know why. Despite the hefty challenges that remain, Rosenberg and others hope this improved protocol can be adapted for other cancers and possibly even immune disorders such as AIDS.

Related sites
Rosenberg paper

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