During a 20-year career in the U.S. Navy, immunologist Carl H. June studied radioactivity, HIV, and bone marrow transplants. But it was the 1996 diagnosis of his wife, Cynthia, with ovarian cancer that galvanized him to look beyond the lab. She died of the disease in 2001. “It gave me a real impetus to make something happen clinically, which is a lot harder than research in mice,” he says. Now a researcher at the University of Pennsylvania, June is drawing on his lifetime of laboratory work to perfect a gene therapy that has drawn attention in the oncology field because it eradicated cancer in two patients with terminal leukemia.
The disease is often treated with a bone marrow transplant, but many patients’ bodies reject the foreign matter. The side effects are “horrendous,” says June, 58, and kill about 20 percent of people who undergo the procedure.
June’s therapy avoids such complications because it uses a patient’s own genetic material—with a few modifications. A doctor first takes the patient’s blood and separates out T-cells, an important immune system component that kills such invaders as cancer cells but is easily overwhelmed by the fast-growing disease. June adds new DNA to the cells, which help them identify CD-19, a molecule that lies on the outside surface of leukemia cells. The foreign DNA is introduced through an inactive HIV virus, which is good at infiltrating T-cells. A separate molecule helps outsmart a signal from the tumor that keeps the T-cells from dividing and creating more attackers.
The first human trial of the therapy—one of three required for regulatory approval—involved three patients with chronic lymphocytic leukemia. Other treatments had failed them, but after the new gene therapy two are in full remission and the third is in partial remission. June and his co-researcher, Bruce L. Levine, reported the results in the New England Journal of Medicine last month. It will be years before the treatment is available to the public, though, and the next step is to have the work replicated by other scientists. The approach is “extremely powerful,” says Stephen M. Gottschalk, a cancer doctor at June’s alma mater, Baylor College of Medicine. “The real challenge is, can you do it in other diseases?”
After obtaining his medical degree from Baylor, June became a researcher at the Naval hospital in Bethesda, Md., where he experimented with new bone marrow transplant techniques to help sailors injured by radioactivity during, say, a nuclear submarine accident. Studying radiation, which kills T-cells, helped him better understand the body’s immune system; observing the difficulty of marrow transplants convinced him there must be a better way to treat certain cancers. He may have found it. “It was clear right away that this new therapy was not a little bit better, it was exponentially better,” he says.