NCT07501156

H3K27M-specific Immune Effector Cells Targeting DMG/DIPG

H3K27M-specific Engineered Immune Effectors (EIE) Targeting Diffuse Midline Glioma/Diffuse Intrinsic Pontine Glioma

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Shenzhen Geno-Immune Medical Institute · Academic / Other
• Sex: All
• Age: 2 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to assess the feasibility, safety and efficacy of H3K27M-specific engineered immune effector (EIE) therapy in patients with high-risk, H3K27M-positive diffuse midline glioma/diffuse intrinsic pontine glioma. Another goal of the study is to learn more about the function of the anti-H3K27M EIE cells and their persistency in patients.

Detailed description

Diffuse midline glioma or Diffuse Intrinsic Pontine Glioma (DIPG) represent one of the most devastating pediatric central nervous system malignancies. Despite decades of clinical investigation, the standard of care remains focal radiotherapy, which offers only transient symptomatic improvement without altering the uniformly fatal disease trajectory. The median overall survival remains approximately 11 months from diagnosis, with five-year overall survival below 1%. No effective salvage therapies exist following disease progression, and conventional cytotoxic chemotherapy has failed to improve outcomes. The identification of the clonal H3K27M mutation in histone H3 as a driver of tumorigenesis has provided a unique tumor-specific antigenic target, distinguishing this entity from adult high-grade gliomas and opening avenues for innovative precision immunotherapy. The H3K27M mutation serves as an ideal immunotherapeutic target due to its uniform expression across tumor cells, its absence in normal healthy tissues, and its critical role in oncogenesis. This study incorporates the production and adoptive transfer of autologous H3K27M-specific EIEs. Peripheral blood mononuclear cells (PBMCs) are collected via leukapheresis and stimulated with H3K27M antigen primed autologous dendritic cells. The resultant EIEs phenotypically characterized for CD8+, CD4+ and CD56+ predominance with antigen specificity. Here, the study aims to evaluate the safety and efficacy of the H3K27M-specific EIEs in DMG/DIPG patients.

Conditions

• Diffuse Midline Glioma or Diffuse Intrinsic Pontine Glioma

Interventions

Type	Name	Description
BIOLOGICAL	H3K27M-EIEs	1 to 2 infusions, once a week, for 1x10\^5\~1x10\^7 EIEs/kg via intravenous injection each time

Timeline

• Start date: 2026-03-18
• Primary completion: 2029-12-31
• Completion: 2030-04-30
• First posted: 2026-03-30
• Last updated: 2026-03-30

Locations

1 site across 1 country: China