Intraventricular B7-H3 CAR T Cells for Diffuse Intrinsic Pontine Glioma: Preliminary First-in-Human Bioactivity and...

Area of Science:

• Oncology
• Immunotherapy
• Pediatric Neuro-oncology

Background:

• Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric brainstem tumor with limited treatment options.
• B7-H3 is a target antigen expressed on central nervous system (CNS) tumors, including DIPG.

Purpose of the Study:

• To evaluate the safety and feasibility of repeated locoregional B7-H3-specific chimeric antigen receptor (CAR) T-cell therapy in children with DIPG.
• To assess preliminary efficacy and immune responses following intracranial CAR T-cell administration.

Main Methods:

• Phase I clinical trial (BrainChild-03) administering repeated locoregional B7-H3 CAR T cells to pediatric patients with recurrent/refractory CNS tumors, including DIPG.
• Monitoring for dose-limiting toxicities, clinical and radiographic outcomes, CAR T-cell persistence in cerebrospinal fluid (CSF), and immune analyte modulation via targeted mass spectrometry.

Main Results:

• The first three evaluable DIPG patients received up to 40 infusions without dose-limiting toxicities.
• One patient demonstrated sustained clinical and radiographic improvement for 12 months.
• Evidence of local immune activation was observed, including persistent CSF B7-H3 CAR T cells and modulation of key immune analytes.

Conclusions:

• Repeated intracranial B7-H3 CAR T-cell dosing is feasible and well-tolerated in pediatric DIPG patients.
• Intracranial delivery of B7-H3 CAR T cells may induce beneficial local immune activation.
• These findings support further investigation of B7-H3 CAR T-cell therapy for DIPG and other CNS tumors.