H3K27M-specific Immune Effector Cells Targeting DMG/DIPG

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

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.

Study Overview

• Status: Recruiting
• Conditions: Diffuse Midline Glioma or Diffuse Intrinsic Pontine Glioma
• Intervention / Treatment: Biological: H3K27M-EIEs

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Lung-Ji Chang, Ph.D; Phone Number: +86 0755-86573763; Email: c@szgimi.org

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-immune Medical Institute
      • Contact: Lung-Ji Chang, Ph.D; Phone Number: +86 0755-86573763; Email: c@szgimi.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Abilities to understand and the willingness to provide written informed consent;
2. ≥ 2 and ≤ 70 years old;
3. Recurrent or refractory diffuse midline glioma or diffuse intrinsic pontine glioma patients with confirmed H3K27M mutation and documented lesions. Patients have received standard care of medication, such as gross total resection with concurrent radio-chemotherapy (~54 - 60 Gy, TMZ). Patients must either not be receiving dexamethasone or receiving ≤ 4 mg/day at the time of leukopheresis;
4. Karnofsky performance score (KPS) ≥ 60;
5. Life expectancy >3 months;
6. Satisfactory bone marrow, liver and kidney functions as defined by the following: absolute neutrophile count ≥ 1500/mm^3; hemoglobin > 10 g/dL; platelets > 100000 /mm^3; Bilirubin < 1.5×ULN; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5×ULN; creatinine < 1.5×ULN;
7. Peripheral blood absolute lymphocyte count must be above 0.8×10^9/L;
8. Satisfactory heart functions;
9. Must be willing to follow the instructions of doctors; Women of reproductive potential (between 15 and 49 years old) must have a negative pregnancy test within 7 days of study start. Male and female patients of reproductive potential must agree to use birth control during the study and 3 months post study.

Exclusion Criteria:

1. A prior history of gliadel implantation 4 weeks before this study start or currently receiving antibody based therapies;
2. HIV positive;
3. Tuberculosis infection not under control;
4. History of autoimmune disease, or other diseases require long-term administration of steroids or immunosuppressive therapies;
5. History of allergic disease, or allergy to immune cells or study product;
6. Patients already actively enrolled in other immune cell clinical study; Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: H3K27M-EIEs	Biological: H3K27M-EIEs; 1 to 2 infusions, once a week, for 1x10^5~1x10^7 EIEs/kg via intravenous injection each time

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of adverse effects after H3K27M-EIE injection	To assess the safety of autologous H3K27M-EIEs in vivo. The percentage of patients who have adverse effects will be evaluated by using the NCI CTCAE V4.0 criteria.	up to one month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of successful H3K27M-EIE generation	The percentage of successful H3K27M-EIE generation, which are derived from subjects and pass the safety test after standard culture procedures, viable for at least one preparation, will be evaluated.	up to one month
Ability of H3K27M-EIE cells to induce cancer-specific reactions	ELISPOT measurement of target-specific T cells in blood sample	after 1 month from H3K27M-EIE cell infusion until 12 months after infusion
Ability of H3K27M-EIE cells inducing anti-cancer reactions	Objective response (complete response (CR) + partial response (PR)) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. CR is disappearance of all target lesions. Any pathological lesions (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	after 1 month from H3K27M-EIE cell infusion until 24 months after infusion

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): April 30, 2030

Study Registration Dates

• First Submitted: March 24, 2026
• First Submitted That Met QC Criteria: March 24, 2026
• First Posted (Actual): March 30, 2026

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: DIPG; H3K27M; EIE
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms; Brain Stem Neoplasms; Infratentorial Neoplasms; Diffuse Intrinsic Pontine Glioma
• Other Study ID Numbers: GIMI-IRB-26003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No