Intra-Tumoral Injections of Natural Killer Cells for Recurrent Malignant Pediatric Brain Tumors

1. Participants must have a histologically-confirmed recurrent or progressive malignant brain tumor including, but not limited to, infant-type hemispheric glioma, gliosarcoma, intracranial sarcoma and WHO Grade II ependymoma.
2. Participants should be candidates for resection of the recurrent tumor and be deemed candidate for placement of an Ommaya reservoir placed intra-cavitary/intra-tumoral; measurable residual tumor after surgery is not required for study entry. Pre-operative imaging needs to estimate that the resection cavity will be at least 2 cm x 2 cm in two dimensions for participants to be eligible.
3. Given the lack of a standard of care treatment for children with recurrent or progressive malignant brain tumors, participants must have completed first-line treatment with radiation and/or chemotherapy prior to participating in this trial if applicable.
4. All participants must be ≥ 1 year of age and ≤ 39 years of age at the time of entry into the study. The first 3 participants must be ≥ 8 years of age and ≤ 39 years of age at the time of entry into the study.
5. Performance Score: Karnofsky ≥ 50 for participants > 16 years of age and Lansky ≥ 50 for participants ≤ 16 years of age. 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.

6. Must have recovered from the acute toxic effects of prior therapy (i.e., NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5, grade 1 or less)

   • An interval of at least 12 weeks must have elapsed since the completion of radiation therapy.
   • Chemotherapy/biologic therapy: All cytotoxic chemotherapy/biologic therapy must be discontinued ≥ 7 days prior to enrollment (except 3 weeks for temozolomide and 6 weeks from last dose of nitrosoureas)
   • Immunotherapy: The last dose of anti-tumor antibody therapy must be at least 3 half-lives or 30 days, whichever is shorter, from the time of enrollment
   • For targeted agents only, participants should have recovered from any toxicity of the agent and have a minimum of 2 weeks since the last dose.
   • For participants who have received prior bevacizumab, at least 4 weeks is required.

7. Organ Function Requirements:

   1. Adequate Bone Marrow Function Defined as:

      • Peripheral absolute neutrophil count (ANC) >750/mm\^3.
      • Platelet count >75,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to registration).

   2. Adequate Renal Function Defined as:

      • A serum creatinine ≤ 1.5 x upper limit normal (ULN) based on age/gender.

   3. Adequate Liver Function Defined as:

      • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin ≤ 3 x ULN or direct bilirubin ≤ 1.5 x ULN.
      • Alanine aminotransferase (ALT) ≤ 3 x ULN.
      • Aspartate aminotransferase (AST) ≤ 3 x ULN.

   4. Adequate Neurologic Function Defined as:

      • Participants with seizure disorder may be enrolled if seizures are well-controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug.
      • Signs and symptoms of neurologic deficit must be stable for ≥ 1 week prior to registration.
8. The effects of Transforming growth factor beta resistant (TGFβi) natural killer (NK) cells on the developing human fetus are unknown. For this reason and because TGFβi NK cells as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 6 months after completion of TGFβi NK cells administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
9. Participants must enroll on PNOC COMP if PNOC COMP is open to accrual at the enrolling institution
10. A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.
11. Corticosteroids: Participants who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration. The patient steroid dose should be no more than a steroid-equivalent of dexamethasone 0.1 mg/kg/day (or maximum 4 mg/day; whichever is the lower dose) at time of enrollment.

Exclusion Criteria:

1. Tumor involvement that would require ventricular or brainstem injection or access through a ventricle or significant risk of ventricular penetration in order to deliver the TGFβi NK cells.
2. Participants undergoing needle or open biopsy.
3. Participants who are receiving any other investigational agents.
4. Women of childbearing potential must not be pregnant or breast-feeding.
5. Evidence of active uncontrolled infection or unstable or severe intercurrent medical conditions.
6. Any medical condition that precludes surgery.
7. Prothrombin time/international normalized ratio (PT/INR) or partial thromboplastin time (PTT) > 1.5 x ULN.
8. Participants with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV), or an auto- immune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible.
9. Evidence of bleeding diathesis or use of anticoagulant medication or any medication which may increase the risk of bleeding. If the medication can be discontinued >1 week prior to NK cell infusion then the subject may be eligible following consultation with the Study Chairs.
10. Participants with significant systemic or major illnesses including but not limited to: congestive heart failure, ischemic heart disease, kidney disease or renal failure, organ transplantation, or significant psychiatric disorder.
11. History or current diagnosis of any medical or psychological condition that in the Investigator's opinion, might interfere with the participants ability to participate or inability to obtain informed consent because of psychiatric or complicating medical problems.

Important note: The eligibility criteria listed above are interpreted literally and cannot be waived.