Immunotherapy for Malignant Pediatric Brain Tumors Employing Adoptive Cellular Therapy (IMPACT)

RECIPIENT SCREENING INCLUSION CRITERIA 1. Diagnosis (select one group): * Group A: New diagnosis of CNS embryonal tumors: medulloblastoma, embryonal tumor with multilayered rosettes, pineoblastoma, atypical teratoid/rhabdoid tumor, and embryonal tumor, not otherwise specified (NOS). * Group B: Radiographic evidence consistent with recurrent ependymoma, with planned or recent re-resection. 2. Age: o Group A: \<5 years of age at enrollment o Group B: \>1 year and \<30 years of age at enrollment 3. Tissue: * Group A: Availability of sufficient fresh or frozen tumor tissue (approximately 50 mg). * Group B: Expectation of sufficient fresh or frozen tumor tissue, in the opinion of study PI or sub-I (based upon radiographic evidence of disease). 4. Non-pregnant: * Group A: N/A * Group B: For female of childbearing potential, must have negative pregnancy test. Common to both groups: 5. Karnofsky or Lansky score of ≥60%. 6. Adequate organ function, defined below: i. ANC ≥750/µL. ii. Absolute lymphocyte count (ALC) \>500/μL. iii. Platelets ≥75K. iv. Bilirubin ≤3xULN. v. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \<5x upper limit of normal (ULN). vi. Serum creatinine ≤1.0 mg/dL or 1.5x ULN for age (whichever is higher). vii. Pulse oximetry \>90% on room air. 7. The patient (if ≥18 years old), or the patient's parent(s)/legal guardian(s) (if the patient is a minor), is capable of providing informed consent. 8. Patient deemed to be of sufficient size to undergo MNC apheresis for TSA-T generation (Groups A and B) and PBSC rescue (Group A only). 9. Patient is a surgical candidate for placement of a Rickham reservoir in the opinion of study PI or medically licensed sub-I. RECIPIENT INCLUSION CRITERIA FOR PROCUREMENT 1\. Karnofsky or Lansky score of ≥60%. 2. Adequate organ function, defined below: i. ANC ≥750/µL. ii. Absolute lymphocyte count (ALC) \>500/μL. iii. Platelets ≥75K. iv. Bilirubin ≤3xULN. v. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \<5x upper limit of normal (ULN). vi. Serum creatinine ≤1.0mg/dL or 1.5x ULN for age (whichever is higher). vii. Pulse oximetry \>90% on room air. 3. Non-pregnant: * Group A: N/A * Group B: For female of childbearing potential (if applicable; see section 2.3.1.6), must have negative pregnancy test. RECIPIENT INCLUSION CRITERIA FOR INITIAL TSA-T ADMINISTRATION AND FOR ADDITIONAL INFUSIONS 1. Applicable to TSA-T infusion #1 only: Group B participants must have histopathologic confirmation of recurrent ependymoma. 2. Karnofsky or Lansky score of ≥60%. 3. Adequate organ function, defined as below: i. Bilirubin ≤3x ULN. ii. AST and ALT ≤5x ULN. iii. Serum creatinine ≤1.0mg/dL or 1.5x ULN for age (whichever is higher). iv. Pulse oximetry \>90% on room air. 4. Applicable to TSA-T Infusion #1 only: Adequate count recovery, as described below, from prior therapies: i. Absolute Neutrophil Count (ANC) \>1000/μL ii. Absolute Lymphocyte Count (ALC) \>500/μL 5. Patients must have received their last dose of: a. Myelosuppressive chemotherapy (if applicable) ≥14 days prior to TSA-T infusion b. Focal radiation (if applicable) ≥14 days prior to TSA-T infusion c. Craniospinal irradiation (if applicable) ≥28 days prior to TSA-T infusion 6. Patients must have recovered from all acute effects of prior surgical intervention/s. 7. Group B female of childbearing potential or male capable of fathering a child (if applicable): Agree to use contraceptive measures during TSA-T treatment participation through 6 months following last administration of TSA-Ts 8. Group B female of childbearing potential (if applicable; see section 2.3.1.6), must have negative pregnancy test. 9. Neurologic status: Patient must have a stable neurologic exam for 2 weeks, on a stable or decreasing dose of steroids, prior to administration of the first dose of TSA-T cells, and stability for 1 week prior to all subsequent infusions. The exams demonstrating stability must be performed by the study team, although these may occur via telemedicine if necessary. Patient must agree to a brief (\<72 hours) course of steroids if the PI or medically-licensed sub-I deems it clinically necessary in the context of clinical deterioration. 10. Presence of a Rickham reservoir and catheter for intracerebroventricular administration of TSA-T therapy, placed \>7 days prior to TSA-T infusion. 11. For patients with programmable VP shunts: Able to tolerate the shunt being closed for at least 4 hours, in the opinion of study PI or medically licensed sub-I. EXCLUSION CRITERIA RECIPIENT SCREENING EXCLUSION CRITERIA 1\. Patients with uncontrolled infections. 2. Patients with known HIV infection. 3. Group A patients with medulloblastoma of the SHH subtype. RECIPIENT EXCLUSION CRITERIA FOR PROCUREMENT 1\. Patients with a fever above 38.0°C. 2. Patients with known HIV infection. 3. Prior immunotherapy with an investigational agent within the 28 days prior to planned date of procurement collection for TSA-T manufacturing. 4\. Patients who will be unable to tolerate the apheresis procedure, including inability to tolerate placement of apheresis line (if applicable), in the opinion of PI or medically licensed sub-I. 5\. Patients who have overly bulky tumors on imaging are ineligible. These include the following: i. Tumor with any evidence of herniation or significant midline shift. ii. Tumor with a significant brainstem component. iii. Patients who are deemed to have overly bulky tumor by the PI of the study. If, due to complications during apheresis or subsequent manufacturing, procurement is repeated at a later date using peripheral whole blood collection, exclusion criterion #4 does not apply. RECIPIENT EXCLUSION CRITERIA FOR INITIAL AND SUBSEQUENT TSA-T INFUSIONS 1. Patients with progressive disease based on most recent evaluation (for subsequent infusions). a. Patients with progressive disease based on most recent evaluation may receive initial TSA-T infusion but would be ineligible if the tumor is found to be progressive before subsequent infusions 2. Patients with uncontrolled infections. 3. Patients who have overly bulky tumors on imaging are ineligible. These include the following: i. Tumor with any evidence of herniation or significant midline shift. ii. Tumor with a significant brainstem component. iii. Patients who are deemed to have overly bulky tumor by the PI of the study. 4. Patients who received ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of TSA-T infusion. 5. Patients receiving steroids (e.g., dexamethasone) at a dose of \>0.05 mg/kg/day. 6. Patients who have non-programmable VP shunts.