CAR T Cells to Target GD2 for DMG

Inclusion Criteria:

1. Age ≥ 2 and ≤ 16 years
2. Tissue diagnosis of H3K27M mutant Diffuse Midline Glioma.
3. Radiographically evident tumour restricted to the brain stem or spinal cord.
4. At least 6 weeks following completion of radiation therapy.
5. At least 3 weeks or 5 half-lives, whichever is shorter, after treatment with agents on other early phase clinical trial
6. Performance status: Karnofsky (age ≥ 10 years) or Lansky (age \< 10) score ≥ 40% allowing for stable neurological deficit due to DMG
7. Absolute neutrophil count ≥1.5 x109/L and platelet count ≥ 100 x109/L
8. Total bilirubin \< 1.5 ULN and ALT \< 2.5 ULN
9. Serum creatine \< 1.5 ULN for age.
10. For post-pubertal subjects agreement to have a pregnancy test, use adequate contraception (if applicable)
11. Written informed consent

Exclusion Criteria:

1. Systemic corticosteroid therapy ≥ 0.05 mg/kg dexamethasone daily (or equivalent) at time of RQR8/huK28Z CAR T cell infusion
2. Tumour involvement of the thalamus or supratentorial lesions, cerebellar vermis or hemispheres (pontocerebellar peduncle involvement is allowed)
3. Clinical or radiological evidence of true tumour progression
4. Active hepatitis B, C or HIV infection
5. Inability to tolerate leukapheresis
6. Pre-existing significant neurological disorder not related to DMG
7. Clinically significant systemic illness or medical condition (e.g., significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of the investigational regimen and its requirements.
8. Any contraindication to lymphodepletion or to the use of Cyclophosphamide or Fludarabine as per the local SmPC
9. Any contraindication to the use of Anticoagulant Citrate Dextrose Solution
10. Any contraindication to Ommaya reservoir insertion (or similar catheter)
11. Known allergy to albumin, DMSO or EDTA
12. Primary immunodeficiency or history of autoimmune disease (e.g., Crohn's, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression /systemic disease modifying agents within the last 2 years
13. Prior treatment with investigational or approved gene therapy or cell therapy products
14. Life expectancy \<3 months
15. Use of rituximab (or rituximab biosimilar) within the last 3 months prior to RQR8/huK28Z CAR T cell infusion
16. Post-pubertal subjects who are pregnant or breastfeeding