On April 16, 2013, Dana and Chris Lee sat bedside at The Children’s Hospital of Philadelphia as their last best hope began to filter through the IV in their 9-year-old’s arm.

Tori had been diagnosed with acute lymphoblastic leukemia (ALL), the most common childhood cancer, as a kindergartner. Since then, she’d relapsed twice. She had never experienced a full year of school. Friends she’d made in the hospital had died. “The pain and suffering of so many families is always around us in this world,” Dana Lee says, “and we were so close to that point of a parent’s worst nightmare.”

Tori is one of 25 children and five adults who traveled to Philadelphia between April 2012 and February 2014 to take part in a study that now has the world’s attention. They came to CHOP and the University of Pennsylvania from around the country, with cancer at a stage previously considered incurable.

Immune cells attack

The patients received cells created from their own immune systems. Scientists re-engineered T cells, the workhorses of the immune system, to recognize and attack an invader that normally flies under their radar:  cancer cells.

The results published in October 2014 in The New England Journal of Medicine are unprecedented: Ninety percent were in complete remission after one month and 67 percent remained in complete remission after six months. The first child to take part has been in remission for more than two years. By comparison, remission rates for the three drugs most recently approved for relapsed ALL are reported at less than 25 percent.

“The patients who participated in these trials had relapsed as many as four times, including 60 percent whose cancers came back even after stem-cell transplants. Their cancers were so aggressive, they had no treatment options left,” says Stephan Grupp, M.D., Ph.D., the oncologist who leads the study at CHOP. “But what we are most excited about is that a number of these children have remained in remission with no further therapy for up to 2½ years. These durable responses we have observed with this therapy are unprecedented.”

Scientists have been trying to engineer T cells to attack cancer cells for more than 20 years, but had difficulty creating cells that would proliferate (multiply) and persist in the body. The cells in the Penn-CHOP study demonstrate a high level of proliferation and persistence. It appears that high-level proliferation can lead to high response rates, while persistence leaves anticancer T cells “on the hunt” and can keep kids in remission.

FDA-designated breakthrough

In July, the U.S. Food and Drug Administration designated CAR T-cell therapy for relapsed ALL a “breakthrough therapy.” It is the first time a personalized cellular therapy for cancer has received this designation, which can help speed the path to approval as a treatment. CAR T-cell therapy studies for relapsed leukemia are now open at other children’s hospitals, with CHOP as the lead center, and there are plans to extend the research to other types of cancer, including relapsed neuroblastoma. Pharmaceutical giant Novartis has licensed rights to the therapy.

For some families who took part in this groundbreaking study, hopes were not realized: There have been deaths. These children and adults contributed to an effort that will save many others.

Dana Lee thinks often of those children who didn’t make it. “I look at Tori and I know that every day is such a gift,” she says.

Last year Tori finished a full year of school with no interruption. She started fifth grade this fall. “Tori is running on the beach,” her mom says. “She’s fearless on the diving board. She has playdates. She is a little girl smiling and doing kid stuff. T-cell therapy gave us this.”