HER2-Specific CAR T-Cell Trial Addresses Pediatric Brain and Spinal Cord Tumors

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Locoregional delivery of chimeric antigen receptor (CAR) T cells has resulted in objective responses in adults with glioblastoma, but the approach has not been evaluated in pediatric patients with brain and central nervous system tumors. The innovative, ongoing phase I BrainChild-01 trial is assessing the safety and efficacy of delivering repetitive doses of T cells into the brain or the cerebrospinal fluid of children and young adults with recurrent or refractory tumors, including patients with diffuse midline gliomas. The findings so far indicate the treatment is feasible and tolerable, reported Vitanza et al in Nature Medicine.

“We are committed to not only finding cures for children and young adults with central nervous system tumors, but to offer more tolerable treatments with fewer long-term side effects. This research is still in its early stages, but promising signs suggest that our approach may be safe,” said lead author Nicholas Vitanza, MD, a neuro-oncologist at Seattle Children’s Hospital.

Brain and spinal cord tumors are the most common pediatric cancer, accounting for approximately one out of four childhood cancer diagnoses. Each year, more than 4,000 brain and spinal cord tumors, which are often fatal, are diagnosed in children and teenagers.

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The CAR T-cell treatment being studied in the trial targets the HER2 protein on cancer cells. The manufactured T cells are infused into the cerebrospinal fluid or in the tumor resection cavity weekly, primarily in the outpatient setting.

Dr. Vitanza and colleagues are the first research group to publish findings on the viability of repetitively delivering CAR T cells directly to the brain in children and young adults. One of the initial three patients in the preliminary dataset was a 19-year-old with a grade 3 localized anaplastic astrocytoma; two other patients, aged 16 and 26 years, had grade 3 metastatic ependymomas. All were diagnosed under the age of 19 and thus had pediatric biology. Patients had undergone at least three tumor-directed surgical procedures, at least one treatment with irradiation, and at least one chemotherapy regimen.

The three patients experienced no dose-limiting toxicities and exhibited clinical evidence—as well as correlative laboratory evidence—of local immune activation within the central nervous system, including high concentrations of CXCL10 and CCL2 in the cerebrospinal fluid. Other advanced correlative studies are ongoing to better understand the activity of the CAR T cells.

BrainChild-01 is the first of three trials seeking to comprehensively target all types of pediatric brain and spinal cord tumors. BrainChild-03 includes patients with diffuse intrinsic pontine glioma (DIPG). It is one of the first CAR T-cell trials in the United States for children with DIPG and was the first study to repeatedly dose CAR T cells intracranially. It is open to patients with DIPG at any time after initial standard radiation, including after their tumor progresses.

All three BrainChild studies are open and enrolling, said Dr. Vitanza, who is the principal investigator for the BrainChild-01 and BrainChild-03 trials. Approximately three dozen children and young adults have been enrolled across all studies.

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