Seattle Children’s Opens Trial for Children and Young Adults With Leukemia That Targets CD22 and CD19 Proteins Simultaneously

Seattle Children’s has opened the first chimeric antigen receptor (CAR) T-cell immunotherapy trial in the U.S. for children and young adults with relapsed or refractory CD19- and CD22-positive acute lymphoblastic leukemia (ALL) that will simultaneously attack two targets on cancer cells. 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.

“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 and lead investigator for the PLAT-05 trial. “In launching a bilateral attack on the 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.”

Earlier Trials

Dr. Gardner and the research team, led by Michael Jensen, MD, 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.

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

In PLAT-02, researchers use gene therapy to reprogram the CAR T cells to recognize and target the CD19 protein that is expressed by most precursor B ALL cells. However, in some patients, the leukemia recurred and evaded the CAR T cells by no longer expressing the CD19 target, and expressed a protein that the CAR T cells were unable to recognize—CD22.

Looking Ahead

With the PLAT-05 trial, researchers will now 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.

“While we’re pleased that we’ve been able to get patients who are very sick into remission, and some have been in remission for more than 3 years, we want all of our patients to be cancer-free for life,” said Dr. Gardner. “That’s what we’re working toward.”

In seeing the promise of CAR T-cell immunotherapy, Seattle Children’s researchers are also working to develop CAR T-cell trials that will target solid tumors, including brain tumors and sarcomas.

“We believe that 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.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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