T cells work by attaching to antigens, distinctive proteins that reside on the surface of tumor cells. Once they lock on, the T cells secrete tumor-destroying hormones. Melanoma cells are coated with an antigen called MART-1.
In an earlier experiment, Rosenberg's team removed white blood cells from patients with metastatic melanoma and isolated the most aggressive tumor-fighting T cells. Those cells were multiplied in the lab and reinjected into patients after their immune systems were cleared using chemotherapy drugs.
The experiments showed promise, but about half the patients didn't have any T cells that were able to target melanoma, Rosenberg said. So he decided to give ordinary T cells the genes they would need to recognize MART-1.
The researchers spliced the genes for making the anti-MART-1 receptor into a disabled retrovirus. Then the retrovirus was let loose on a few million white blood cells that had been removed from each melanoma patient.
As the virus infected the cells, the new gene was transferred into the T cells. When the cells multiplied, the subsequent generations also had the anti-MART-1 receptor, Rosenberg said.
The team used chemotherapy to wipe out the patients' existing immune cells, then replaced them with the genetically modified cells.
Some patients showed hardly any uptake of the new genes, but half the patients wound up with the new gene in at least 20% of their T cells.
After three months, eight patients still had detectable levels of the genetically modified T cells in their systems.
In one patient, the engineered T cells grew to make up about two-thirds of his immune system. Though previous treatments with powerful drugs and surgery had failed to stem his cancer, the gene therapy shrank an enlarging tumor on his lung until it disappeared altogether.
Another patient, 53-year-old Mark Origer, had tried drugs, surgery and an experimental vaccine before enrolling in the gene therapy trial. By the time he had his first checkup about a month after getting the souped-up T cells, his tumors had shrunk in half.
"It was euphoric," said Origer, who was diagnosed with melanoma in 1999. "I had waited so many years to find something that was working."
The T cells eradicated the tumor under his arm and shriveled another tumor in his liver by 89%. He has been cancer-free since the remaining mass was surgically removed in October.
