Illuminate: A Clinical Study Evaluating CAR T Immune Cell Therapy (BCB-276) for Patients With Diffuse Intrinsic Pontine Glioma (DIPG).

This study will evaluate BCB-276, an investigational B7-H3-targeted Chimeric Antigen Receptor (CAR) T cell therapy, in children and young adults with diffuse intrinsic pontine glioma (DIPG). DIPG is a rare and aggressive brain tumor with limited treatment options. CAR T cell therapy uses a patient's own immune cells that are changed in a laboratory to recognize and attack cancer cells. The purpose of this study is to determine whether BCB-276, when given after completion of standard radiation therapy, is safe and can improve survival for patients with DIPG. To participate, individuals must be between 1 and 26 years of age when they join the study, have a diagnosis of DIPG, and enroll for treatment within 6 weeks of completing initial radiation therapy. Participants must not have received prior anti-cancer therapy beyond radiation with or without temozolomide prior to joining this study. BCB-276 is administered intraventricularly (into the fluid around the brain), which requires placement of a catheter for treatment. BCB-276 is given every 2 weeks at a research center over a period of several months (approximately 7-8 months). Participation includes travel to a study site, procedures to support treatment administration, sample collection, and ongoing monitoring for safety and effectiveness, with follow-up visits lasting up to about 2 years.

Inclusion Criteria: * Participants must be aged 1 and ≤ 26 years and weigh ≥10kg. * Diagnosis of Diffuse Intrinsic Pontine Glioma (DIPG) based on imaging, with or without biopsy confirmation consistent with high-grade glioma or diffuse midline glioma * Able to tolerate leukapheresis and other study procedures in the opinion of the Investigator. * Central Nervous System (CNS) reservoir catheter present prior to first dose of study drug. * Participant must have completed standard radiation therapy within 6 weeks of enrollment for participation. * Performance Status of ≥ 60; mild to moderate restriction or better. Lansky (under 16 years of age) or Karnofsky (16 years of age or older). * Adequate organ function and overall clinical status to participate, including stable or improving neurologic symptoms. * Participants of childbearing/fathering potential must agree to use highly effective contraception from the time of enrollment through 12 months following the last T cell infusion. * Participants with ventriculoperitoneal (VP) shunts need to have a programable system and be able to tolerate temporary adjustment of the shunt required for study treatment. * Participant must meet all other health and safety criteria defined in the study protocol. * Participant and/or authorized legal representative willing to provide consent/assent for study participation, including participation in the 15-year long term follow up period. Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study: * Previous tumor-directed therapy or treatment-directed clinical study other than standard radiation with or without temozolamide. * Evidence of metastatic disease. * Requirement of high or increasing doses of corticosteroids prior to participation. * Severe swallowing difficulties or other significant clinical conditions that may interfere with participation. * Presence of an active malignancy other than DIPG. * Active or uncontrolled human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection based on protocol-required laboratory testing. * Pregnant or breastfeeding. * Presence of any condition that, in the Investigator's opinion, would prohibit the participant from undergoing treatment under this protocol.