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Building a Better Tumor Killer
31 August 2006 (All day)
In a first for gene therapy, researchers have successfully treated cancer patients by genetically modifying their immune cells to attack tumors. Although the treatment worked in only two of 17 patients, the researchers say this proof of concept, reported online today in Science, should pave the way for more gene-therapy cancer cures.
Steven Rosenberg's group at the National Cancer Institute (NCI) in Bethesda, Maryland, has been working on ways to rev up immune cells to vanquish cancer for 2 decades. A few years ago, the researchers removed tumor-attacking immune cells called T cells from melanoma patients, grew more in the lab, and reinjected them into the patients. The influx of additional tumor-attacking cells pushed the cancer to regress in about half the patients (Science, 25 October 2002, p. 850). But only about half of melanoma victims have these tumor-fighting T cells, and the cells are very scarce in other kinds of cancer.
So for 17 patients with advanced melanoma who didn't have tumor-fighting T cells and had failed existing treatments, Rosenberg's team tried gene therapy. The researchers removed normal T cells from the patients' blood, then gave them a powerful guidance system: a molecule that sticks out from the T cell and homes in on melanoma tumor cells. The gene that codes for this molecule was ferried into the cells via a harmless retrovirus. The researchers then injected these modified cells back into the patients.
In 15 of the patients, the injected cells thrived and made up at least 10% of their total T cells weeks later. Two men who had even higher levels of the modified T cells experienced a dramatic recovery. In one, a liver and armpit tumor that had developed from spreading melanoma cells shrank, and in the other a lung tumor disappeared. Both men remain healthy 18 months after treatment.
That success rate is low, Rosenberg admits, but he adds, "this is just a start." Rosenberg's group is now working on a half-dozen ways to improve the treatment, including adding molecules that are better at finding cancers. The team is also hoping to test T cells modified to attack breast, lung, and colon tumors.
"The technology will get better," agrees cancer gene therapy researcher Carl June of the University of Pennsylvania. One important result is that the treatment didn't seem to cause a serious autoimmune response as a side effect, he adds. "I'm very happy to see this," he says. "This shows the basic safety. That's really good news for the field."