Engineered immune cells that target the H3K27M mutation in diffuse midline glioma and DIPG

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

This trial will test whether a patient's own immune cells, engineered to recognize the H3K27M mutation, can be safely given and help people aged 2–70 with H3K27M‑positive diffuse midline glioma or DIPG.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 2 Years to 70 Years
• Sex: All
• Sponsor: Shenzhen Geno-Immune Medical Institute (other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT07501156 on ClinicalTrials.gov

What this trial studies

This phase 1/2 interventional program uses each patient's own immune cells collected by leukapheresis and stimulated with H3K27M peptide‑primed autologous dendritic cells to expand H3K27M‑specific engineered immune effector (EIE) cells. After manufacturing and quality testing, the autologous H3K27M‑EIEs are infused back into patients with recurrent or refractory H3K27M‑positive diffuse midline glioma or DIPG, with monitoring for safety, persistence of the infused cells, and signs of anti‑tumor activity. Key eligibility includes confirmed H3K27M mutation, age 2–70 years, adequate organ function, KPS ≥60 and limited steroid use, and the protocol includes serial imaging and laboratory assessments to track outcomes and adverse events. The study aims to define feasibility, toxicity, and preliminary efficacy signals to guide further development of this tumor‑specific adoptive cell therapy.

Who should consider this trial

Good fit: Ideal candidates are patients aged 2–70 with recurrent or refractory H3K27M‑positive diffuse midline glioma or DIPG, adequate organ function, KPS ≥60, life expectancy >3 months, and who can tolerate leukapheresis and limited steroid use (≤4 mg/day).

Not a fit: Patients without the H3K27M mutation, those with poor performance status or very short life expectancy, uncontrolled organ dysfunction, or unable to travel to the trial site are unlikely to gain benefit.

Why it matters

Potential benefit: If successful, H3K27M‑specific EIE therapy could offer a tumor‑targeted treatment that slows progression and improves survival with limited damage to normal tissues.

How similar studies have performed: Preclinical studies and a few early‑phase immunotherapy trials targeting H3K27M have shown biological activity and safety signals, but robust clinical benefit has not yet been established.

Eligibility criteria

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.

Where this trial is running

Shenzhen, Guangdong

• Shenzhen Geno-immune Medical Institute — Shenzhen, Guangdong, China (RECRUITING)

Study contacts

• Study coordinator: Lung-Ji Chang, Ph.D

Conditions: Diffuse Midline Glioma or Diffuse Intrinsic Pontine Glioma, EIE, DIPG, H3K27M