B7-H3.CD28Z.CART in CNS Neoplasms

Pre-screening Inclusion Criteria: * Participants must have histologically and/or molecularly confirmed CNS embryonal tumor (see eligible tumor types below), OR ependymoma that is recurrent/progressive following standard of care treatment. --Eligible CNS embryonal tumor types include: * Medulloblastoma * Atypical Teratoid Rhabdoid Tumor (ATRT) * Embryonal Tumor with Multilayered Rosettes (ETMR) Pineoblastoma * Other CNS embryonal tumor types, at the discretion of the study chair (or designee) * Participants must have adequate pre-trial tumor material available to determine B7- H3 expression status. Tumor tissue from the most recent resection or biopsy of recurrent disease is preferred. If unavailable, tumor tissue from prior recurrences or from time of initial diagnosis is acceptable. Biopsies will not be performed for participation in this research trial or for research purposes. * Pre-screening IHC Consent: All participants ≥ 18 years of age must be able to give informed consent. For participants \<18 years of age, their legal authorized representative (LAR) (i.e. parent or guardian) must give informed consent. Pediatric participants will be included in age-appropriate discussion and written assent will be obtained for those ≥10 years of age, where appropriate. If a minor becomes of age during participation of this study, they will be asked to reconsent as an adult. Inclusion Criteria: * Participants must have histologically and/or molecularly confirmed CNS embryonal tumor (see eligible tumor types below), OR ependymoma that is recurrent/progressive following standard of care treatment. --Eligible CNS embryonal tumor types include: * Medulloblastoma * Atypical Teratoid Rhabdoid Tumor (ATRT) * Embryonal Tumor with Multilayered Rosettes (ETMR) * Pineoblastoma * Other CNS embryonal tumor types, at the discretion of the study chair (or designee) * B7-H3 expression: Demonstration of B7-H3 expression with H score greater than 100 by immunohistochemistry (IHC) is required. * Age: greater than or equal to two (2) years of age and less than or equal to 21 years of age. The first participant treated at each dose level within each stratum (Standard Risk and High Risk) will be ≥ 6 years of age when feasible. * Disease status: Participants must have evaluable disease in the central nervous system to be eligible. Evaluable disease includes either measurable OR non-measurable disease, defined as follows: --Measurable disease (contrast-enhancing or non-enhancing tumor) * Clearly defined lesional margins with two perpendicular diameters of at least 10mm, OR * At least two times (in both perpendicular diameters) the MRI slice thickness, plus the interslice gap --Non-measurable disease (tumor that is too small to be accurately measured) * Lesion that is measurable in only one perpendicular dimension, OR * Lesion that is less than 10mm in at least one perpendicular dimension, OR * Lesion that is less than two times the MRI slice thickness, plus the interslice gap * Note: Leptomeningeal (LM) disease is considered non-measurable but evaluable. * Performance status: Karnofsky performance status ≥60% for participants ≥16 years of age and Lansky performance status ≥60% for participants \<16 years of age (see APPENDIX A PERFORMANCE STATUS CRITERIA). NOTE: Participants with neurologic deficits must have a stable neurologic exam for seven (7) days prior to enrollment. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * Life expectancy of greater than 12 weeks * Prior therapy: Participants must have received prior standard of care therapy, including maximal safe surgical resection, radiation therapy and/or standard chemotherapy, and is recovered from all acute treatment-related toxicities (defined as ≤ Grade 1 or stable) from all prior therapy before entering this study There is no upper limit to the number of prior therapies allowed, but must have received all standard curative options for their tumor type. * Participants must meet the following washouts prior to enrollment: * Radiation therapy - Participants must have had their last fraction of: ---Craniospinal irradiation, whole brain radiation therapy, or radiation therapy to \>50% of the pelvis or spine \>28 days prior to enrollment ---Focal irradiation (small port) \>14 days prior to enrollment * At least 14 days since any prior cytotoxic chemotherapy * At least 7 days since any biologic antineoplastics, tyrosine kinase inhibitor, targeted agent * At least 21 days or 5 half-lives (whichever is shorter) since any investigational antineoplastic or disease-directed agent (but at least 28 days from prior investigational antineoplastic vaccine therapy) * At least 21 days since any monoclonal antibody therapy * At least 90 days since any systemic inhibitor/stimulatory immune checkpoint therapy * At least 28 days from prior autologous stem cell transplantation, with no ongoing toxicities * At least 14 days after peg-filgrastim and 7 days for hematopoietic growth factor support * Steroid use: Must not require concurrent systemic steroid therapy, although physiologic corticosteroid replacement therapy for management of pituitary/adrenal insufficiency and/or topical administration (e.g. inhaled or dermatologic) is allowed. Use of topical, ocular, intranasal, or inhaled corticosteroids are permitted per PI discretion. * Participants must have adequate organ function, as defined below --Adequate bone marrow function * Hemoglobin ≥ 8 g/dL * Absolute neutrophil count (ANC) ≥ 1000 cells/uL * Absolute lymphocyte count (ALC) ≥ 150 cells/uL * Platelets ≥100,000/uL (unsupported, defined as no platelet transfusion within 4 days) * Adequate renal function defined as creatinine within normal limits for age OR creatinine clearance (as estimated by Cockcroft Gault Equation for participants ≥ 18yo and Bedside Schwartz for participants \<18yo) ≥70mL/min * Maximum Serum Creatinine mg/DL ---6 months to 1 year Male 0.5 Female 0.5 ---1 to \< 2 years Male 0.6 Female 0.6 ---2 to \< 6 years Male 0.8 Female 0.8 * 6 to \< 10 years Male 1 Female 1 * 10 to \< 13 years Male 1.2 Female 1.2 * 13 years to \< 16 years Male 1.5 Female 1.4 * 16 years Male 1.7 Female 1.4 * Adequate hepatic function * Serum ALT/AST ≤3.0 upper limit of normal (ULN) * Total bilirubin ≤1.5mg/dL, except in subjects with confirmed Gilbert's syndrome * Adequate cardiac function --Ejection fraction ≥50% or fractional shortening ≥28%, measured by echocardiography * Adequate pulmonary function * No evidence of dyspnea at rest * Pulse oximetry \>92% whilst breathing room air * Adequate neurologic function * Participants with seizure disorders on anticonvulsants may be enrolled if seizures are well controlled (no seizure activity within 7 days prior to enrollment) * Nervous system disorders (CTCAE v6.0) resulting from prior therapy must be ≤ Grade 2, with the exception of decreased tendon reflex (DTR; any Grade eligible). Participants with neurological deficits should be stable for a minimum of 7 days prior to enrollment. (A baseline detailed neurological exam should clearly document the neurological status of the participant prior at enrollment). * Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization are not considered to be of childbearing potential) * Participants of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for one year after receiving the preparative lymphodepletion regimen, or for as long as B7- H3.CD28Z.CART cells are detectable in peripheral blood or CSF, whichever is later. * Participant or parent of participant or legally recognized representative must be able to sign a written informed consent document. Pediatric participants will be included in age-appropriate discussion and written assent will be obtained for those ≥10 years of age, where appropriate. Exclusion Criteria: * Participants with bulky tumor are ineligible. Bulky tumor is defined as: * Tumor with diameter of \>5cm in one dimension on T2/FLAIR sequence * Tumor with evidence of clinically significant midline shift or uncal herniation * Tumor that, in opinion of the site investigator, shows significant mass effect in either the brain or spine * Participants with clinical or radiological evidence of brain herniation. * Participants who have received other B7-H3 targeted cellular therapies. Other prior cellular therapies are eligible, including immune checkpoint inhibition and vaccine therapy. These prior therapies should be discussed with the study chair (or designee) prior to participant enrollment. * Concurrent illness * Participants with any prior immunodeficiency or history of autoimmune disease requiring systemic steroids/ immunosuppressive medication/ disease-modifying agents within the last two (2) years. * Uncontrolled (Grade 3) bacterial, viral, fungal, or other infection. * Ongoing infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative PCR and/or nucleic acid testing. * Evidence of severe or uncontrolled systemic disease (e.g. Grade 3 significant cardiac, pulmonary, hepatic, renal or other organ dysfunction) that in the judgement of the principal investigator is likely to interfere with assessment of safety or efficacy of the investigational regimen and its requirements. * Known sensitivity or allergy to any of the agents/reagents used in this study (i.e. DSMO, cyclophosphamide, fludarabine) * History of severe hypersensitivity reaction to compounds of similar chemical or biologic compositions to any agent used in the study or in the manufacturing of cells. * Concomitant medications * Current systemic corticosteroid therapy * Note, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency will be allowed. * Participants who are receiving any other anti-cancer or investigational drug therapy are ineligible. * Participants who have received the last vaccination of a live vaccine ≤ 30 days prior to the start of treatment are ineligible. * Ongoing use of dietary supplements, alternative therapies or extreme diets, or any medication not approved by the study chair (or designee). * Any other condition which in the principal investigator's opinion makes the individual clinically unsuitable to participate in this trial, or which would jeopardize compliance with the protocol, or would make it difficult to interpret adverse events or study data.