CELL INTELLIGENCE · 肿瘤细胞治疗研究

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.

主要终点：Overall Survival · Up to 24 months from date of enrollment · Overall Survival (OS) as defined as time from the date of enrollment to death from any cause (up to 24 months from date of enrollment).
次要终点：Safety and Tolerability of BCB-276；Radiographic Response to BCB-276；Presence of BCB-276 in Cerebrospinal Fluid (CSF)；Progression-Free Survival (PFS)

• BCB-276 CAR-T therapy for newly diagnosed DIPG patients post-radiation therapy · EXPERIMENTAL · Participants will receive up to 15 intraventricular administrations of BCB-276 delivered every 14 days (+/- 2 days) for an approximate total duration of 30 weeks.

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.