C7R-GD2.CAR T Cells for Patients With GD2-expressing Brain Tumors (GAIL-B)

Procurement Inclusion Criteria: Cohort 1: 1. Histologically confirmed, GD2-expressing newly diagnosed DMG/HGG (including pontine) or confirmation of H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence. OR Histologically confirmed, GD2-expressing recurrent, refractory, or progressive DMG/HGG (except pontine) or confirmation of positive H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available. OR Recurrent, refractory, or progressive high-grade CNS tumor with confirmed GD2-expression. Examples include: medulloblastoma "CNS embryonal tumors, AT/RT, ependymal tumors, diffuse gliomas or glioneuronal tumors. Cohort 2: Recurrent, refractory, or progressive pontine HGG with confirmed GD2-expression or H3K27-altered DMG 2. Tumors less than 5 cm in maximum dimension at enrollment 1. Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study 2. Tumors with \>25% increase in size on post-radiation imaging may be reassessed with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently ≤ 25% increased compared with pre-irradiation MRI. 3. Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked 3. Measurable disease on at least 2 dimensions on MRI 4. Age 12 months to 25 years 5. Functional score (Karnofsky/Lansky) ≥ 50 expected at infusion (≥60 for cohort 2) Procurement Exclusion Criteria: 1. Patients who are pregnant or breast feeding 2. Any patient with other risk factors for whom administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator. Treatment Inclusion Criteria Cohort 1: 1. Histologically confirmed, GD2-expressing newly diagnosed DMG/HGG (including pontine) or confirmation of H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available. Newly diagnosed is defined as prior to radiographic progression or recurrence. OR Histologically confirmed, GD2-expressing recurrent, refractory, or progressive DMG/HGG (except pontine) or confirmation of positive H3K27 alteration if sufficient tissue for GD2 staining by IHC is not available. OR Recurrent, refractory, or progressive high -grade CNS tumor with confirmed GD2-expression. Examples include: medulloblastoma, CNS embryonal tumors, AT/RT, ependymal tumors, diffuse gliomas, or glioneuronal tumors. Cohort 2: Recurrent, refractory, or progressive pontine H3K27-altered for DMG or HGG with confirmed GD2-expression. 2. Tumors less than 5 cm in maximum dimension at enrollment 1. Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks post-radiotherapy remain eligible for study 2. Tumors with \>25% increase in size on post-radiation imaging may be reassessed with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently ≤ 25% increased compared pre-irradiation MRI 3. Tumors with sizes between 5 and 5.5 cm are eligible if the tumor was surgically debulked 3. Measurable disease on at least 2 dimensions on MRI 4. Central line (PICC or other) and Ommaya reservoir or VP shunt in place or planned to be placed. Central line/PICC may be omitted for cycles that do not include lymphodepletion 5. Age 12 months to 25 years 6. Functional score (Karnofsky/Lansky) ≥ 50 (≥60 for cohort 2) 7. Patients must have completed standard of care radiation therapy at least 4 weeks prior to administration of investigational agent. If bevacizumab was administered for management of radiation necrosis, therapy must be completed at least 4 weeks prior to administration of investigational agent. 8. Stable neurologic exam for 7 days prior to enrollment 9. Stable or decreasing dose of steroids (max. allowable dose of dexamethasone is 0.1 mg/kg/day over the past 7 days prior to infusion of investigational therapy) 10. Organ function: 1. ANC \> 1000 cells/ul 2. Platelet count \> 100,000 cells/ul 3. Total bilirubin \< 1.5x ULN 4. ALT and AST \< 5x ULN 5. Serum creatinine or kidney within 2x ULN for age Treatment Exclusion Criteria 1. Patients who received any other forms of immunotherapy ≤ 42 days before administration of investigational agent 2. Patients who received colony-stimulating factors within 14 days prior to administration of lymphodepletion 3. Patients receiving any concurrent anti-cancer therapy (treatment must occur at least three half-lives following prior anti-cancer therapy) 4. Patients who are pregnant or breast feeding 5. Any patient with other risk factors for whom administration of investigational agent is deemed not in the patient's best interest, in the opinion of the investigator.