Research Shows Seattle Children’s Pioneering Immunotherapy Trial May Be Feasible to Combat Pediatric Brain and Spinal Cord Tumors

An innovative clinical trial led by Dr. Nicholas Vitanza, a neuro-oncologist at Seattle Children’s, shows promise that delivering cancer-fighting chimeric antigen receptor (CAR) T cells directly into the brain for children and young adults with recurrent or refractory brain and central nervous system (CNS) tumors may be feasible and acceptable.

The results, published today in Nature Medicine, are the first findings of the BrainChild-01 immunotherapy clinical trial from Seattle Children’s Therapeutics. BrainChild-01 is the first of three such studies that focus entirely on all types of brain and spinal cord tumors in children.

Seattle Children’s Therapeutics, a unit in Seattle Children’s research division, is bringing promising CAR T-cell immunotherapies to the first clinical trials of their kind for children. As a new, not-for-profit therapeutic development company, it is committed to devising and testing next-generation cell and gene therapies for childhood diseases so that children receive the medicines they deserve.

“This research is still in its early stages, but promising signs suggest that our approach may be safe,” Vitanz said. “We are determined not only to find a cure for children and young adults with CNS tumors, but also to offer more acceptable treatments with fewer long-term side effects.”
Brain and spinal cord tumors are the most common childhood cancer, accounting for about one in four childhood cancers. More than 4,000 brain and spinal cord tumors are diagnosed in children and teens each year. Some of these tumors have a high mortality rate.

CAR T-cell immunotherapy is an experimental treatment that stimulates the immune system to fight disease. The treatment reprograms T cells (white blood cells in the immune system that fight disease) to activate and kill cancer cells. In this trial, treatment targets the human erb-b2 receptor tyrosine kinase 2 (HER2) protein on childhood and young adult cancer cells with limited treatment options. The protein is expressed by common brain tumors in children. The T cells are delivered directly into the CNS space by infusion into the fluid surrounding the brain and spinal cord, or into the cavity after tumor resection. T-cell doses are given weekly, primarily in the outpatient setting.
In the first results published today, the researchers describe a preliminary assessment of their Phase I clinical trial, making them the first group to publish the first findings on the viability of repeatedly delivering CAR T cells directly to the brain. in children and young adults.

The study ultimately aims to answer a series of questions, primarily whether it is safe to administer repeated doses of T-cell therapy to the brain or the fluid surrounding the brain and spinal cord of children or young adults. It also aims to assess the best dose of therapy for children and young adults with CNS tumors, and seeks to answer whether T-cell therapy works against brain and CNS tumors.

The approach “supports the feasibility of generating HER2CARs for repeated dosing regimens and suggests that their repeated CNS release may be acceptable,” the authors wrote in the study.
In addition, in the BrainChild-01 study, researchers found evidence of a CAR T cell-generated inflammatory response in the patient’s cerebrospinal fluid (CSF) and one patient had neuroimaging findings of local immune activation just after CAR T cell dosing. Other advanced correlative studies are underway to better understand how well and for how long the CAR T cells fight the tumor.

Faces of Research at Seattle Children’s Research Institute June 7-8, 2018 in Seattle, WA. Photo by Andy Rogers Images

“This research is great news for kids like me who fear relapse without known treatment,” said Avery Berg, who was previously treated for a rare, aggressive brain cancer at Seattle Children’s and is still cancer-free. “This trial offers hope on the horizon for a potential new treatment option for children with brain cancer.”
Seattle Children’s is an international leader in efforts to better treat cancer in children, adolescents and young adults by equipping the immune system with the ability to recognize cancer cells as targets. It has the most comprehensive pediatric CAR T cell immunotherapy program in the world, meaning it treats more childhood cancers using CAR T cell therapies than any other facility.

In addition to BrainChild-01, Seattle Children’s has two additional open clinical trials for relapsed or refractory CNS tumors, BrainChild-02 and BrainChild-03. BrainChild-03 includes patients with diffuse intrinsic pontine glioma (DIPG), a universally fatal brain tumor. The BrainChild-03 study is one of the first CAR T cell studies in the United States for children with DIPG and was the first study in which CAR T cells were repeatedly dosed intracranially to a child with DIPG. It is open to patients with DIPG at any time after their first standard irradiation, including after their tumor is evolving.

All three BrainChild studies are now open and enrollment is possible, said Vitanza, who is the principal investigator of the BrainChild-01 and BrainChild-03 studies, with nearly three dozen children and young adults enrolled in all of the studies.

Seattle Children’s CAR T-cell immunotherapy research and the BrainChild clinical trials are supported by a community of generous donors.

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