Seattle Children’s Hospital Opens CAR T-Cell Immunotherapy Trial in Pediatric Leukemia


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Seattle Children’s Hospital has opened the first chimeric antigen receptor (CAR) T-cell immunotherapy trial in the United States for children and young adults with relapsed or refractory CD19- and CD22-positive acute lymphoblastic leukemia (ALL). With this more robust defense, researchers hope the new experimental therapy, first being investigated in the phase I Pediatric Leukemia Adoptive Therapy (PLAT-05) trial, will ultimately be able to cut the rate of relapse following CAR T-cell therapy by almost half.

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“This is an exciting time where we’re at the forefront of advancing the CAR T-cell immunotherapy field by pioneering strategies to improve long-term outcomes for children and young adults,” said Rebecca Gardner, MD, an oncologist at Seattle Children’s Hospital and lead investigator for the PLAT-05 trial. “In launching a bilateral attack on cancer cells, we hope this trial will help us develop a T-cell therapy that leads to long-term remission for many more of our patients.”

With the help of gene therapy, in the PLAT-05 trial, researchers will be able to reprogram CAR T cells to detect and destroy leukemia cells by targeting both the CD19 and CD22 proteins upfront. If the cancer evolves to no longer express CD19, the CAR T cells can still attack the cancer through the identification of the CD22 protein. Researchers hope to enroll about 20 patients in the trial over the next year and a half.

Learning From Other PLAT Trials

Dr. Gardner and the research team, led by Dr. Mike Jensen at the Ben Towne Center for Childhood Cancer Research at Seattle Children’s Research Institute, are launching PLAT-05 based on what they learned from their previous CAR T-cell immunotherapy trials. In phase I of the ongoing PLAT-02 trial, which Dr. Gardner also leads, 93% of patients with relapsed or refractory ALL achieved complete initial remission. However, about 50% of those patients relapsed after the experimental therapy. With relapse presenting a challenge in CAR T-cell trials across the country, Seattle Children’s Hospital researchers are dedicated to improving the therapy with the goal of long-term remission for all patients and, ultimately, a cure.

Researchers found that patients in the PLAT-02 trial relapsed for one of two reasons: They lose persistence of their reprogrammed CAR T cells, or the leukemia evolves to circumvent the CAR T cells. Although the PLAT-03 “T-cell booster” trial that Seattle Children’s Hospital opened in May aims to address the disappearance of T cells, PLAT-05 may be the key to preventing the cancer from escaping the CAR T cells.

The researchers are also working to develop CAR T-cell trials that will target solid tumors. “We believe T-cell immunotherapy holds tremendous potential to combat leukemia and several other types of pediatric cancer,” said Dr. Gardner. “Leukemia is just the tip of the iceberg, and we hope to develop a therapy that can be given to patients as a first line of defense, greatly reducing the side effects of cancer treatment.” ■


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