In a remarkable manipulation of the human immune system, researchers have trained white blood cells to protect patients against a particular viral infection.
The investigators transfused the white cells into five patients with bone-marrow transplants and found that the cells remained alive and able to kill virus-infected cells for at least 12 weeks. The cells came from the donors of the bone marrow, so they were compatible with each recipient's newly acquired immune system, which is derived from the cells of the bone marrow.
Although the experiment involved few patients, immunologists and cancer specialists say its success opens the door to new treatments for cancer and viral infections among patients who have received a bone-marrow transplant. The researchers are already beginning a study with AIDS patients who have received bone-marrow transplants to see if trained white blood cells can help them fight the AIDS virus.
The researchers, from the Fred Hutchinson Cancer Center in Seattle and the University of Washington, reported the results for the first three patients in today's issue of the journal Science. Study Breaks New Ground
"This is a really beautiful piece of work," said Dr. Drew Pardoll, a cancer immunologist at Johns Hopkins University in Baltimore. "It's going to definitely open the door for some exciting studies to come, both in viral infections and in cancer."
In their study, Dr. Stanley Riddell, Dr. Philip Greenberg and their colleagues extracted white blood cells from bone-marrow donors and trained the cells by growing them in the presence of a protein from cytomegalovirus, the cause of a pneumonia that is often fatal to patients who get bone-marrow transplants. This protein is the one that white cells normally recognize on the surface of cells infected with cytomegalovirus, and it can provoke the white cells to attack.
The researchers infused billions of these cells into each leukemia patient who had received a bone-marrow transplant and was temporarily without a working immune system. The investigators removed white cells from the patients periodically and tested them to see if they could fight cytomegalovirus infections. The cells remained able to fight the virus for at least 12 weeks, the researchers found.
Normally, such white blood cells, known as killer T-cells, cruise through the body, on surveillance for cells that are infected or malignant. The killer T-cells recognize these cells because they have abnormal proteins on their surfaces. When they see such a protein, killer T-cells react by proliferating vigorously, creating a colony of killer cells that will search for any cell carrying that protein and destroy it. Finding an Immunity Booster
The key to harnessing killer T-cells for immune therapy has been to identify the abnormal proteins that jog the T cells into action. Last year, Dr. Greenberg and his colleagues found the protein from cytomegalovirus that provokes T-cells to destroy them. Several researchers are also finding such proteins on the surfaces of cancer cells. And investigators have found that essentially every protein from the AIDS virus stimulates killer T-cells.
Dr. Greenberg explained that once his group of researchers had found the cytomegalovirus protein, they were set to go with an attempt to protect patients with bone-marrow transplants. The investigators grew killer T-cells in the laboratory in the presence of that protein and a hormone, interleukin-2, that stimulates the growth of immune cells. Then they infused these T cells back into the patients, providing them with immunity to the virus.
Dr. Greenberg said his group was expanding the study to include an additional 15 patients with bone-marrow transplants.
But bone-marrow transplant patients have an immune deficiency that is short-lived, Dr. Greenberg said. Others, like people with AIDS, who have a persistent lack of immunity, would need a treatment that lasts indefinitely. Dr. Greenberg said that his group was attempting to provide a more permanent immunity by adding a gene for interleukin-2 to the T cells.
"We are attempting to design a T cell that, when it recognizes a target cell, will get a signal not just to kill it but to make more T cells," he said. In that way, the T cells would perpetuate themselves. While the AIDS virus infects T cells, it affects a different class of T cells than the killer cells.
In addition, Dr. Greenberg said, he and his colleagues are also starting to look at killer T-cell transfers as a potential treatment for AIDS itself. They will be teaching T cells to fight the human immunodeficiency virus, which causes AIDS, and then will infuse these cells into people infected with H.I.V. in an effort to help them fight off infection.
That new study involves H.I.V.-infected patients who developed lymphomas and who had bone-marrow transplants to treat that type of cancer. Dr. Greenberg cautioned that the study was highly experimental.