A child who got CAR-T cancer therapy is still disease-free 18 years later

About 18 years ago, a 4-year-old girl with a rare nerve cell cancer received an infusion of immune cells that were genetically engineered to fight the disease. Since then, she has remained cancer-free, possibly making her the longest-surviving patient with cancer who received this tailored treatment, researchers report February 17 in Nature Medicine.

As part of a clinical trial, the girl received CAR-T cell therapy, a treatment that requires removing some of a patient’s immune cells and programming them to target and kill cancer cells before returning them. Since 2017, seven CAR-T cell therapies have been approved by the U.S. Food and Drug Administration for a few blood cancers. But solid tumors, like the girl’s neuroblastoma, have been harder to treat with this technology.

This is because solid tumors, which account for approximately 90 percent of all cancers, are tougher to penetrate and are equipped with molecules that can hinder the engineered cells, says Helen Heslop, a physician-scientist at Baylor College of Medicine and Texas Children’s Hospital in Houston.

“Neuroblastoma is the first solid tumor where there looks like there could be curative effects with CAR-T cells,” says cancer immunotherapist Carl June, who was not involved in the study. “It’s really exciting, I think, to see this happen.”

Heslop’s team recruited 19 children with neuroblastoma — 11 with actively growing cancer and eight who were at high risk of relapsing. From 2004 to 2009, all 19 were infused with CAR-T cells. Within seven years of treatment, 12 patients relapsed and died. Of the seven survivors, five were at risk of relapse when treated and were disease-free 10 to 15 years later. The other two had actively growing cancer at the time they were infused with the treatment. One was still in remission eight years later, but stopped participating in the study at that point; the other is the 18-year survivor.

“I think now we need to know why some people progressed and some people didn’t,” says June, who works at the University of Pennsylvania Perelman School of Medicine. Perhaps in patients who didn’t continue to benefit, either the engineered cells didn’t stick around long enough, or the tumor lost the protein the cells were targeting.

Since this study was done, Heslop says, she and other investigators have added special molecules to CAR-T cells to make them last longer and track down tumors better. In 2023, researchers at Bambino Gesù Children’s Hospital in Italy published a study in which nine of 27 patients with neuroblastoma had no signs of cancer six weeks after receiving next-generation CAR-T cells. Five of those patients were cancer-free about one to two years later. Longer-term results should be out soon.

“Hopefully those patients, too, will have sustained benefit and survive long-term,” says Heslop. While a great deal more research would be needed, she says this is a glimmer of hope that neuroblastoma, and perhaps other solid tumors, could be treatable with CAR-T.