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Improving CAR T-Cell Immunotherapy in Children, Young Adults

Improving CAR T-Cell Immunotherapy in Children, Young Adults

Chimeric antigen receptor (CAR) T-cell immunotherapy is now reaching a pivotal point where researchers hope to determine if they can extend its benefits. Researchers at Seattle Children's Research Institute announced the first-in-human clinical trial aimed to extend remission for children and young adults with leukemia treated with CAR T-cell immunotherapy.

The phase I results of Seattle Children’s Pediatric Leukemia Adoptive Therapy (PLAT-02) trial demonstrated CAR T-cell immunotherapy was highly effective and 93% of patients with relapsed or refractory acute lymphoblastic leukemia (ALL) achieved complete initial remission. However, the relapse rate was approximately 50% and now researchers are hoping they can overcome that problem.

The new phase I pilot study (PLAT-03) will examine the feasibility and safety of administering a second T-cell product intended to increase the long-term persistence of the patient’s CAR T cells that were reprogrammed to detect and destroy cancer. In the PLAT-03 trial, patients will receive booster infusions of a second T-cell product called T antigen-presenting cells (T-APCs). The T-APCs have been genetically modified to express the CD19 target for the cancer-fighting CAR T cells to recognize.

In the new pilot study, patients will receive a full dose of T-APCs every 28 days. All the patients will receive at least 1 dose and in some cases up to 6 doses. By stimulating the CAR T cells with a steady stream of target cells to attack, researchers hope the CAR T cells will reactivate and this will help ensure their persistence and lead to long-term remission.

PLAT-03 is now open to patients who first enroll in phase II of Seattle Children’s PLAT-02 trial and who are also identified as being at risk for early loss of their reprogrammed CAR T cells, or those who lose their reprogrammed CAR T cells within 6 months of receiving them.

The PLAT-03 trial is one of several trials that Seattle Children’s researchers are planning to open within the next year aimed at further improving the long-term efficacy of T-cell immunotherapy. In addition to a current T-cell immunotherapy trial that is open for children with neuroblastoma, researchers also hope to expand this promising therapy to other solid tumor cancers.

“We are pleased to be at a pivotal point where we are now looking at several new strategies to further improve CAR T-cell immunotherapy so it remains a long-term defense for all of our patients,” said Rebecca Gardner, MD,  who is an oncologist at Seattle Children's and the lead investigator of the PLAT-02 trial. “We’re also excited to be working to apply this therapy to several other forms of pediatric cancer beyond ALL, with the hope that T-cell immunotherapy becomes a first line of defense, reducing the need for toxic therapies and minimizing the length of treatment to only weeks.”

Patients treated in PLAT-02 had less than a 20% chance of survival upon enrollment using current treatments. The ultimate goal of these studies are to develop a novel therapy that can be offered to newly diagnosed cancer patients. This approach is appealing because it may help patients avoid other toxic therapies and minimize the length of treatment from months or years to only weeks.


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