#10: Immune 
Supercells Purge Leukemia

A new therapy turns leukemia patients’ own cells into cancer 
assassins. It may one day help fight other cancers, too.

By Veronique Greenwood|Thursday, January 05, 2012

Oncologist David Porter was walking across the quad at the University of Pennsylvania in September 2010 when he got the call. One of his advanced-stage leukemia patients had low levels of electrolytes and compromised kidney function, the caller reported. A spiking fever, chills, and nausea suggested a classic case of flu.

Porter knew it wasn’t the flu. Something far more momentous was happening. “His disease must be responding,” he thought. Just two weeks earlier Porter and his colleague Carl June had injected three leukemia patients with genetically modified versions of their own immune cells to seek and destroy their cancer. The flulike symptoms were the first sign that these engineered supercells were working, and it only got better from there.

Last August Porter and June reported in The New England Journal of Medicine that within a month they had driven the cancers in two of three leukemia patients into remission. “What we couldn’t do with chemotherapy,” Porter says, “we were able to do in four weeks with immune therapy.” The trial opens the door for new therapies for the thousands of people with leukemia and perhaps, down the road, the millions suffering from other cancers.

Leukemia is cancer of the blood, usually of white blood cells called B cells. When healthy, B cells are an integral part of the immune system, making antibodies that recognize and fight pathogens. But cancerous B cells are not only useless for fighting infection, they also grow out of control, leading to swollen lymph nodes, anemia, and frequent infections. Though many people can survive leukemia with chemotherapy and other drugs, Porter’s patients had not responded to any of the available treatments.

Porter and June’s strategy was to enable the body’s own immune system to eliminate the cancer cells. Their weapon of choice was another type of 
white blood cell, the T cell, which identifies foreign pathogens and unleashes swarms of killer chemicals, called cytokines and chemokines, to eradicate them. T cells do not attack cancerous B cells because they recognize them as part of the self. But if the researchers could teach T cells to target B cells specifically, perhaps immune therapy could do what chemotherapy could not. The target Porter and June ultimately chose was CD19, a protein on the surface of B cells only, discovered by researchers at Harvard Medical School in the 1980s. Targeting CD19 would wipe out healthy B cells along with the cancer even after the therapy, Porter and June knew. But they reasoned that they could help the body compensate with periodic injections of immunoglobulin, a cocktail of antibodies from thousands of blood donors used to fight infection in patients with compromised immune systems.

Armed with a strategy and a target, Porter and June spent the past several years honing their approach, including developing a synthetic virus to deliver genes that would program T cells to hunt down CD19. In August 2010, backed by $1 million in private funding, they began a three-person trial. They drew blood from the patients, isolated the T cells, and infected them with the engineered virus. The patients received injections of their genetically modified 
T cells over three days, and then the waiting game began.

It took less than a month for the results to surpass Porter’s loftiest expectations. When injected, the three patients were each carrying more than two pounds of tumor. For years—in one case, a decade—their cancer had withstood every treatment doctors could throw at it. Yet four weeks after receiving the modified T cells, nearly all of it was gone. A thousand cancer cells died for every T cell injected, the team calculates. Two of the patients are now in complete remission, and the third has far fewer leukemia cells than before.

Porter, June, and their colleagues suddenly became the center of attention. Since many forms of leukemia involve B cells, the CD19-focused approach should theoretically work for about three-quarters of blood cancer patients. Some scientists believe the treatment might be useful for a slate of other cancers as well. No wonder the team from Penn has been besieged by entreaties for entry into clinical trials and other sorts of help.

The researchers are taking it slow, however. Porter and his team know not to look too far ahead after such a small trial. They will have to address side effects such as the flulike symptoms and the kidney failure that occurred in one patient due to all the dead cells the body had to cleanse from the blood. Porter will also monitor the patients’ long-term health; since they lack healthy B cells, they may require lifelong immunoglobulin to help resist other cancers, immune disorders, and infectious disease.

The team’s primary goal at the moment is figuring out what made the treatment work so well. They may be the maestros who gave the orchestra the sheet music, but they are not sure which instruments led to the successful sound. A week after the release of Porter’s 2011 paper, a team conducting a similar study at Memorial Sloan-Kettering Cancer Center reported only moderate success in a nine-patient trial. Porter and June are now participating in a new trial, funded by the National Cancer Institute, that will administer about a dozen patients a fifty-fifty mixture of cells from the Penn and Sloan-Kettering groups. Watching how the cells behave will let the teams see how they differ and draw conclusions about why.

Jumping from leukemia to other cancers will require even more time. “The challenge is finding targets that exist on other types of cancer cells but not on normal cells,” says pediatric oncologist Stephan Grupp of the Children’s Hospital of Philadelphia, who worked with Porter on testing the treatment in mice. It will not be easy, but Porter is hopeful that one day doctors specializing in other cancers will experience what he did when examining one of his leukemia patients not long after that phone call on the quad: He felt under the man’s arm for his lymph nodes, which had been enlarged by the cancer for years. Porter was astonished. The swelling was gone.

Comment on this article
ADVERTISEMENT

Discover's Newsletter

Sign up to get the latest science news delivered weekly right to your inbox!

ADVERTISEMENT
ADVERTISEMENT
Collapse bottom bar
DSCNovCover
+

Log in to your account

X
Email address:
Password:
Remember me
Forgot your password?
No problem. Click here to have it emailed to you.

Not registered yet?

Register now for FREE. It takes only a few seconds to complete. Register now »