• Diagnosis: Histologically confirmed diagnosis of medulloblastoma or other primary CNS embryonal tumor according to 2021 CNS WHO Classification (5th edition)

‣ Other acceptable CNS embryonal tumors include:

⁃ Embryonal Tumor with Multilayered Rosettes (ETMR)

⁃ Pineoblastoma

⁃ Atypical Teratoid/Rhabdoid Tumor (ATRT) of the CNS

⁃ CNS neuroblastoma, FOXR2-activated

⁃ CNS Embryonal Tumor NOS

• Recurrent/Refractory Disease: History of relapsed and/or recurrent disease defined as tumor progression or recurrence following initial diagnosis and upfront treatment with curative intent, or failure to achieve disease control with standard curative-intent therapy.

• GPC2 Positive: H-score ≥ 100 by IHC staining performed on the (Prescreening Protocol IRB-78780, PI: Katherine Ryan, DO) at Stanford Clinical Anatomic Pathology Lab for GPC2 from a tumor sample any time since initial diagnosis.

• Evaluable Disease: Evaluable disease as per radiographic findings and/or positive cerebrospinal fluid cytology within 28 days of enrollment.

• Patients with VP shunts: Patients with pre-existing ventriculo-peritoneal (VP) shunt devices must have a programmable shunt device to enroll on this study. A VP shunt is not a requirement for this study.

• Prior therapy: No limit to the number of prior treatment regimens. Toxicities due to prior therapy must be stable or recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia, nutritional support measures, electrolyte abnormalities, or those not impacting the investigator's ability to assess treatment emergent toxicities).

• The following wash-out periods apply at time of enrollment:

• a. At least 6 weeks following craniospinal radiation therapy. i. At least 14 days wash-out needed following small volume radiotherapy (i.e., Stereotactic Radiosurgery (SRS)).

• b. At least 21 days or 5 half-lives (whichever is shorter) must have elapsed since any prior systemic therapy, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives.

• c. At least 28 days following bevacizumab treatment. d. At least 30 days following any investigational drug.

• Age: ≥ 12 months to ≤ 30 years of age at time of enrollment The first 3 subjects treated with GPC2-CAR T cells must be ≥ 3 years old at time of infusion

• Performance Status: Subjects ≥ 16 years of age must have Karnofsky ≥ 60%. Subjects \< 16 years of age must have Lansky scale 60%; or ECOG performance status ≤ 2 (see Section 11.3).

• Normal Organ and Marrow Function \[supportive care is allowed per institutional standards, i.e., filgrastim, transfusion\]

∙ Hemoglobin ≥ 8 g/dL

‣ Absolute Neutrophil Count (ANC) ≥ 1,000/μL

‣ Platelet count ≥ 75,000/μL, with no platelet transfusion within 96 hours prior to enrollment

‣ Absolute lymphocyte count (ALC) ≥ 150/μL

‣ PT/INR, PTT ≤ 1.5 x ULN for age

∙ Adequate renal, hepatic, cardiac, and pulmonary function defined as:

‣ Serum creatinine \< 1.5 x ULN for age and gender, OR creatinine clearance or GFR (radioisotope or iothalamate) ≥ 70 mL/min/1.73 m2

‣ Serum ALT or AST ≤ 3x ULN

‣ Total bilirubin ≤ 1.5 mg/dL, unless subject has Gilbert's Syndrome

‣ Cardiac ejection fraction ≥ 45%

∙ No evidence of physiologically significant pericardial effusion as determined by an ECHO

∙ No clinically significant ECG findings

∙ No clinically significant pleural effusion

∙ Pulse oximetry ≥ 92% on room air, OR forced vital capacity ≥ 50% of predicted value

⁃ Not Pregnant: Females of childbearing potential must have a negative pregnancy test.

⁃ Contraception: Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four (4) months after receiving the preparative regimen or for as long as CAR T cells are detectable in peripheral blood.

⁃ Must provide informed consent. All subjects ≥ 18 years of age must be able to give informed consent. For subjects \<18 years old or adults with limited decision-making capacity, their legal authorized representative (LAR) (i.e., parent or guardian) must give informed consent. Pediatric subjects will be included in age-appropriate discussion and assent will be obtained for those \> 7 years of age, when appropriate. If a minor becomes of age during participation of this study, he/she will be asked to reconsent as an adult.