Loc3CAR: Locoregional Delivery of B7-H3-CAR T Cells for Pediatric Patients With Primary CNS Tumors

Inclusion Criteria: Screening Eligibility Age ≤ 21 years of age Primary CNS tumor with measurable disease For Cohort A, must have evidence of relapsed or refractory non-brainstem CNS tumor For Cohort B, must meet one of the following criteria: Adequate tumor tissue from for central pathology review Brainstem high-grade neoplasm with available imaging for central review Life expectancy of > 12 weeks Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines Exclusion Criteria: Screening Eligibility All Participants 1. Clinically significant medical disorders that could compromise their ability to tolerate protocol therapy or would interfere with study procedure Inclusion Criteria: Procurement and T-cell Production Eligibility Age ≤ 21 years of age Primary CNS tumor with measurable disease and meets criteria for either Cohort A or B: Cohort A: relapsed/refractory non-brainstem CNS primary tumor AND tumor is B7-H3 positive Cohort B: brainstem high-grade neoplasm AND tumor is: B7-H3 positive OR H3K27-altered diffuse midline glioma OR radiographically-confirmed classic/typical DIPG Estimated life expectancy of >12 weeks Karnofsky or Lansky performance score ≥50 Participant of childbearing/child-fathering potential agrees to use contraception For females of childbearing age: Not pregnant with negative serum pregnancy test Not lactating with intent to breastfeed Chemotherapy/biologic therapy must be discontinued ≥ 7 days prior to enrollment The last dose of antibody therapy (including check point inhibitor) must be at least 3 half-lives or 30 days, whichever is shorter At least 30 days from most recent cell infusion prior to enrollment. All systemically administered corticosteroid therapy must be stable or decreasing for ≥1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg/m2/day Meets eligibility for apheresis, or has an apheresis product previously collected at a FACT-accredited program Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines Exclusion Criteria: Procurement and T-cell Production Eligibility Participant has a non-programmable ventricular shunt that could compromise study therapy Known primary immunodeficiency or acquired immunodeficiency. Known HIV positivity Severe intercurrent bacterial, viral or fungal infection Rapidly progressive disease Known underlying medical condition for which participation in this trial would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments. Adult patient, Parent, or legal guardian is unwilling or unable to provide consent for participation in a 15 year long-term follow up study. Inclusion Criteria: Treatment Eligibility Cohort A Relapsed/refractory non-brainstem CNS primary tumor Tumor must be considered B7-H3 positive Cohort B Brainstem high-grade neoplasm. Must meet one of the following criteria Tumor is considered B7-H3 positive H3K27-altered diffuse midline glioma Radiographically-confirmed classic/typical DIPG Must complete standard radiation prior to Loc3CAR treatment and be a minimum of 6 weeks post-completion of radiation therapy All participants Age ≤ 21 years old Primary CNS tumor with measurable disease Available autologous T-cell product that has met GMP release criteria Participant has a CNS reservoir catheter (e.g., Ommaya) Participant is ≥ 5 days from CNS surgery, including catheter placement The following treatments must be discontinued for the specified duration prior to treatment enrollment: Radiation therapy: ≥ 6 weeks Bevacizumab: ≥ 28 days Cytotoxic chemotherapy: ≥ 21 days Biologic agents: ≥ 7 days Antibody therapy: ≥ 3 half-lives or 30 days (whichever is shorter) Cellular therapy: ≥ 30 days Investigational agent: ≥ 3 half-lives or 30 days (whichever is shorter) Corticosteroids: All systemically administered therapy must be stable or decreasing for ≥ 1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg/m2/day Estimated life expectancy of >8 weeks Karnofsky or Lansky performance score ≥ 50 Echocardiogram with a left ventricular ejection fraction > 50% Adequate organ function Adequate laboratory values Taking anti-seizure medication, or agrees to initiate anti-seizure medication Recovered from acute toxicities from prior therapy Male participants of child-fathering potential agree to use contraception Female participants of childbearing potential: Negative serum pregnancy test within 7 days prior to infusion Not lactating with intent to breastfeed If sexually active, agrees to use birth control until 3 months after T-cell infusion. Male partners should use a condom Adult patient, parent or legal guardian can understand and is willing to sign a written informed consent document according to institutional guidelines Exclusion Criteria: Treatment Eligibility Participant has a non-programmable ventricular shunt that could compromise study therapy Known primary immunodeficiency or acquired immunodeficiency. Known HIV positivity Severe intercurrent bacterial, viral or fungal infection Myocardial infarction, unstable angina, New York Heart Association class III and IV congestive heart failure, myocarditis, or ventricular arrhythmias requiring medication within 6 months prior to study entry Receiving therapy outlined above during the 'wash-out' period Rapidly progressing disease Received any live vaccines within 30 days Known underlying medical condition for which participation in this trial would not be in the best interest of the participant or that could prevent, limit or confound protocol assessments Adult patient, Parent, or legal guardian is unwilling or unable to provide consent for participation in a 15 year long-term follow up study