The researchers are trying to figure out why the technique worked so well for two patients but not the others. As the experiment went on, the researchers got better at inserting the modified genes at a time when they were multiplying rapidly. That almost certainly helped some patients boost the proportion of modified genes in their systems, Rosenberg said.
Now he and his colleagues are working on a more powerful T cell receptor that does a better job of recognizing melanoma tumors. They are also trying to come up with new retroviruses that can insert genes into immune cells with greater efficiency.
Antigens have been identified for several other cancers, and Rosenberg's team has isolated the genes for some of the corresponding T cell receptors.
"We're most excited about the possibility to use it in general for other kinds of cancers," Rosenberg said. "We hope to start treating patients with other cancers within the next several months."
Other attempts to fight cancer with gene therapy have shown more modest results.
Some researchers have inserted new genes directly into tumors to replace ones that are no longer able to prevent dangerous cells from multiplying. Another approach involves embedding genes into tumor cells so they are easier for immune cells to find. Neither approach has worked as a stand-alone treatment.
The results of Rosenberg's study should give a boost to the field of gene therapy, said Dr. Ted Friedmann, president of the American Society of Gene Therapy and director of the gene therapy program at UC San Diego.
In the 1990s, gene therapy was considered the next revolution in medicine. But a pair of high-profile deaths in clinical trials tainted the field.
Jesse Gelsinger, an 18-year-old with a rare genetic disorder called ornithine transcarbamylase deficiency, died in 1999, four days after researchers injected him with a virus containing modified genes.
A few years later, European scientists treated 11 boys with X-SCID, popularly known as "bubble boy" disease, which leaves victims without an immune system. The gene transfer worked, but three French boys developed leukemia as a result of the treatment, and one of them died.
"We've been hyping gene therapy for a long time," Rosenberg said. "This is the first example of where we can actually use it to treat a cancer patient."
*
karen.kaplan@latimes.com
