Late last week National Public Radio and others reported on a University of Pennsylvania study published in the New England Journal of Medicine describing a dramatic gene-therapy treatment for leukemia. Here, two University of Colorado Cancer Center investigators comment on what looks to be a big payoff of gene therapy techniques that have been in development for over 20 years.

Gene therapy uses a virus to transport engineered genetic material inside a cell. Image courtesy of NIH.


Don Bellgrau, PhD, CU Cancer Center investigator and professor of immunology at the CU medical school and National Jewish Health, explains how U-Penn’s treatment works:

Your body’s T-cells act as seek-and-destroy ‘bots, recognizing foreign cells and killing them without killing your own cells. But because leukemia cells are the evil children of your own cells, your T-cells generally don’t recognize them as foreign and so don’t kill them. The U-Penn researchers changed that.

“First they took the T-cells out of a patient, inserted genes that allow these T-cells to recognize the leukemia cells, grew these reengineered T-cells successfully, and then transferred them back into the patient,” Bellgrau says. Once in the body, these augmented T-cells recognized and killed the leukemia.

The patients in this study hadn’t responded to or had become resistant to other therapies and so this cutting-edge gene therapy was a treatment of last resort. Of the three patients treated, two lost all signs of leukemia and one improved.

“They probably didn’t expect it to be so spectacularly successful as it’s been,” Bellgrau says.

Jerry Schaack, PhD, CU Cancer Center investigator and associate professor of microbiology at the University of Colorado School of Medicine, says gene-therapy treatment for leukemia is “still a blunt instrument, but the results are very exciting. Basically there was a tumor that is not easily treated and they wiped it out.”

The treatment isn’t without its risks: “The potential downside is that in addition to knocking out the mutated B-cells that make up the leukemia, you knock out your healthy B-cells and thus your antibody response,” says Schaack. The indiscriminate loss of B-cells may make patients less able to fight off future infections.

Also, in some ways, it’s as if researchers replaced leukemia with a similarly detrimental monoculture of reengineered T-cells.

“But if the persistence of these engineered T-cells leads to problems they can insert a suicide gene in these T-cells that makes them either easy targets for destruction by another drug, or makes them self-destruct once their work is done,” Bellgrau says.

Still, “risks notwithstanding, it seems as if these patients were happy to trade a prognosis for only six months or a year more of life for potential consequences down the line,” Bellgrau says. “If these re-engineered T-cells continue to proliferate in the body, then this patient will be fine for a long amount of time. That’s a surprise and it’s very cool.”