⁃ Age ≤ 21 years of age

⁃ Primary CNS tumor

⁃ 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 primary tumor resection or biopsy for central pathology review (i.e., B7-H3 expression evaluation by immunohistochemistry \[IHC\] or H3K27M mutation if pontine lesion)

‣ Has a diagnosis of diffuse midline glioma that harbors a mutation associated with this entity (e.g. H3K27M)

‣ Has presumptive/suspected brainstem high-grade neoplasm with available imaging for central imaging 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

⁃ Age ≤ 21 years of age

⁃ Primary CNS tumor with measurable or evaluable 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: Diffuse midline glioma AND tumor is:

⁃ B7-H3 positive if non-pontine

• OR H3K27-altered diffuse midline pontine 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, from the time of enrollment

⁃ 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/m\^2/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

‣ Cohort A

• Relapsed/refractory non-brainstem CNS primary tumor

• Tumor must be considered B7-H3 positive

‣ Cohort B

• Diffuse Midline Glioma - Must meet one of the following criteria

‣ Tumor is considered B7-H3 positive

⁃ H3K27-altered diffuse midline pontine 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 or evaluable disease

⁃ Available autologous T-cell product that has met GMP release criteria

⁃ Participant has a CNS reservoir catheter (e.g., Ommaya) or programmable shunt

⁃ First CAR T cell infusion is planned/scheduled ≥ 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/m\^2/day. Corticosteroid physiologic replacement therapy for management of pituitary/adrenal axis insufficiency and/or topical administration (e.g. inhaled or dermatologic) is allowed.

⁃ Estimated life expectancy of \>8 weeks

⁃ Karnofsky or Lansky performance score ≥ 50

⁃ Echocardiogram with a left ventricular ejection fraction ≥ 50%

‣ Adequate renal function defined as calculated creatinine clearance or radioisotope GFR ≥ 50 mL/min/1.73m\^2.

‣ Adequate pulmonary function defined as forced vital capacity (FVC) ≥50% of predicted value or pulse oximetry ≥90% on room air.

‣ Total Bilirubin ≤3 times the upper limit of normal for age.

‣ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 times the upper limit of normal for age.

‣ Hemoglobin \>8.0 g/dL (can be transfused).

‣ Platelet count \>50,000/mm\^3 (can be transfused).

‣ Absolute neutrophil count (ANC) ≥1000/uL.

‣ Taking anti-seizure medication, or agrees to initiate anti-seizure medication prior to starting study therapy.

‣ Has recovered from all NCI CTAE grade III-IV, non-hematologic 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