Brain and Spinal Cord Tumors of Childhood: Developing Curative Therapies

Technology Overview

Dr. Nicholas Vitanza

Central nervous system (CNS) tumors are the leading cause of childhood cancer death. Diffuse intrinsic pontine glioma (DIPG), a CNS cancer, usually occurs in children under age 10 and is often fatal within one year of diagnosis. Substantial surgical resection is rarely an option because DIPG occurs in a critical brain region responsible for basic functions such as breathing. The current standard of care is palliative radiotherapy, which extends median survival to only 11 months.

The main research goal of pediatric neuro-oncologist Nicholas Vitanza, MD, is overcoming obstacles to curing pediatric CNS cancers, including DIPG. Getting therapeutic agents across the blood-brain barrier is a well-known issue. Dr. Vitanza understands that even when therapies reach the brain, such as through direct introduction into the intracranial space, they do not behave as they do in the rest of the body. This space, which is separate from the body’s main circulatory system, presents unique challenges for cancer treatment. The Vitanza Lab has a range of innovative approaches to meet these challenges.

Directing CAR T cells to brain and spinal cord tumor targets

Chimeric antigen receptor (CAR) T cells are effective against leukemias, which occur in the blood, a natural T-cell environment. In the brain and spine, CAR T cells need extra direction to find their targets. DIPG cells overexpress the cell-surface protein B7-H3, so Dr. Vitanza and team developed CAR T cells that target this cancer marker.

The engineered CAR T cells are entering a phase 2 registration trial based on significant benefits in preclinical studies and promising phase 1 trial findings. The studies established doses for intracranial introduction of the B7-H3 CAR T cells and demonstrated signs of therapeutic benefit for some patients.

The phase 2 clinical trial of B7-H3 CAR T cells arose from one of the world's largest programs for developing and clinically testing CAR T-cell therapy for pediatric CNS tumors, led by Dr. Vitanza. Beyond DIPG, the B7-H3 CAR T cells have potential applications in other pediatric brain tumors, in adult glioblastomas, and for CNS manifestations of the autoimmune disease lupus.

Enhancing targeting of therapies

Dr. Vitanza's phase 1 clinical trials of CAR T cells for CNS cancers discovered another tumor vulnerability that could improve treatment of these tumors. Specifically, intracranial CAR T-cell treatment raises cerebrospinal fluid levels of the chemokine CXCL10, likely produced by activated T cells, tumor cells, and other components of the tumor immune microenvironment.

The Vitanza Lab developed B7-H3 CAR T cells that overexpress the CXCL10 receptor CXCR3-A. The engineered CAR T cells show increased migration toward CXCL10 in vitro. In vivo, CXCR3-A overexpression on T cells increases their tumor targeting and the survival of patient-derived xenograft animal models.

An additional feature of CXCR3-A-overexpressing CAR T cells is that their activation at tumors causes higher local cytokine expression that attracts more CAR T cells. This reaction creates a positive feedback loop that further boosts treatment effectiveness. The evolving technology of engineering CAR T cells to migrate to a tumor-related chemokine has applications in a variety of CNS cancers.

Combining therapies with intracranial CAR T cells

To further enhance the effectiveness of CAR T cells for pediatric CNS cancer treatment, Dr. Vitanza is combining B7-H3-targeted CAR T-cell therapy with anticancer drugs such as ONC206 and histone deacetylase complex inhibitors. These orally administered drugs have shown some effectiveness alone against DIPG. The Vitanza Lab showed that combining ONC206 with B7-H3 CAR T cells enhanced the drug’s cytotoxicity against DIPG cells in vitro and extended survival of patient-derived xenograft animal models.

The Vitanza Lab has expertise in developing and working with patient-derived models, syngeneic immunocompetent models, and related resources including cell lines and other animal models. As Scientific Director of the Brain Tumor Research Program at Seattle Children’s Research Institute and a founder of the clinical-stage biotech company BrainChild Bio, Dr. Vitanza is interested in industry partnerships on innovative approaches to treating pediatric CNS cancers. He is a leading expert in developing tolerable regimens for pediatric brain tumors that must be treated in the intracranial space. Dr. Vitanza has deep expertise rigorously testing these approaches in randomized controlled clinical trials.

Stage of Development

• Preclinical in vitro
• Preclinical in vivo
• Clinical trials

Partnering Opportunities

• Sponsored research agreement
• Consultation agreement
• Licensing Agreements
• Investigator-initiated clinical trials
• Tissue sample access
• Cell line access
• Animal model access

Publications 

Vitanza, N, Song E., Timpanaro A, et al. Engineered CXCR3-A expression enhances the trafficking and efficacy of intracerebroventricularly delivered B7-H3-targeting CAR T cells against diffuse intrinsic pontine glioma. Nat Comm, in press.

Vitanza NA, Ronsley R, Choe M, et al. Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial. Nat Med. 2025;31(3):861-868.

Timpanaro A, Song EZ, Toumi R … Vitanza NA. Preclinical efficacy of combinatorial B7-H3 CAR T cells and ONC206 against diffuse intrinsic pontine glioma. bioRxiv. 2025; Article 2025.09.01.673023.

Timpanaro A, Song EZ, Amwas N … Vitanza NA. Evolving CAR T-cell therapy to overcome the barriers in treating pediatric central nervous system tumors. Cancer Discov. 2025;15(5):890-902.

Pinto N, Albert CM, Taylor MR … Vitanza NA, et al. STRIvE-02: A first-in-human phase I study of systemically administered B7-H3 chimeric antigen receptor T cells for patients with relapsed/refractory solid tumors. J Clin Oncol. 2024;42(35):4163-4172.

Gust J, Cole BL, Ronsley R … Vitanza NA, et al. Locoregional infusion of EGFR806-CAR T cells for recurrent or refractory pediatric CNS tumors: Results of the completed BrainChild02 phase 1 clinical trial. Neuro Oncol. 2025;27(8):2170-2181.

Learn More

• Dr. Nicolas Vitanza, Seattle Children's
• Dr. Nicolas Vitanza, Seattle Children's Research Institute 
• The Vitanza Lab