Each patient will receive up to 12 cycles of TGFβi NK cell infusions. Each cycle will be of 4 weeks duration. During the first 3 weeks, TGFβi NK cells will be infused once weekly. The 4th week will be a rest week. TGFβi NK cell infusions should be delivered at least 3 days apart (e.g., Friday of Week 1 and Monday of Week 2). Dose will be escalated in an inter-patient stepwise fashion consisting of 3 dose levels.

A cycle is 28 days (4 weeks) consisting of weekly infusions of UD TGFβi NK cells via Ommaya or a programable ventriculoperitoneal (VP) shunt for three weeks followed by one week of rest. The dose-limiting toxicity (DLT) period is the first 28 days (4 weeks). A DLT is defined as any event that is at least possibly attributable to the TGFβi NK cell product and that occurs from the time of initial NK cell infusion through the end of the first cycle (28 days). Patients with stable or improved disease will receive up to 12 cycles of TGFβi NK cell infusions.

Inclusion Criteria:

Diagnosis:

Recurrent, refractory, or progressive malignant CNS tumor

• Patients with a histologically confirmed diagnosis of a CNS tumor that is recurrent, progressive, or refractory with the exception of diffuse midline gliomas (DMG) or Diffuse Intrinsic Pontine Gliomas (DIPG). All tumors must have histologic verification at either the time of diagnosis or recurrence.

• Patients should be deemed candidate for placement of an Ommaya reservoir placed intra-cavitary/intra-tumoral or a programable VP shunt.

• Measurable residual tumor after surgery is not required for study entry.

• Resection cavity needs to be at least 2 cm x 2 cm in two dimensions on imaging for patients deemed as candidates for an intratumoral infusion via an Ommaya reservoir.

  • Performance score: Lansky score of 50 or greater if ≤ 16 years of age or a Karnofsky score of 50 or greater if > 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.
  • Adequate bone marrow function, without transfusion or growth factors within 21 days of NK cell administration.
  • Adequate liver function
  • Adequate Renal Function
  • Prothrombin time/international normalized ratio
  • Patients of child-bearing potential must agree to use adequate contraception
  • Adequate neurologic function defined

Prior Therapy:

• Chemotherapy

  • All patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days of nitrosourea.
  • For patients who have received prior bevacizumab, at least 6 weeks must have elapsed prior to enrollment.

• Biologic or investigational agent (anti-neoplastic, non-myelosuppressive):

  • Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent ≥ 14 days prior to study enrollment.
  • For agents with known adverse events occurring beyond 14 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
  • At least 12 weeks since the completion of any immunotherapies or cell therapies.

• Radiation Therapy

  • Focal radiation therapy > 6 weeks prior to enrollment.
  • Craniospinal irradiation >12 weeks.

• Stem Cell Transplant.

Patient must be:

• ≥ 6 months since allogeneic stem cell transplant prior to enrollment with no evidence of active graft vs. host disease.

• ≥ 3 months since autologous stem cell transplant prior to enrollment.

  • Growth Factors

• Patients must be off all colony- forming growth factor(s) for at least 1 week prior to enrollment (e.g., filgrastim, sargramostim or erythropoietin).

• 2 weeks must have elapsed if patients received long-acting formulations.

  • Corticosteroids

• Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment.

Exclusion Criteria:

• Patients with intra- or extra-CNS metastasis or multi-focal disease.
• Patients with diffuse midline gliomas or Diffuse Intrinsic Pontine Gliomas (primary or recurrent).
• Pregnant or lactating patients.
• Participants who are receiving any other investigational agents.
• Evidence of active uncontrolled infection or unstable or severe intercurrent medical conditions.
• Any medical condition that precludes surgery.
• Patients 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.
• Evidence of bleeding diathesis or use of anticoagulant medication or any medication which may increase the risk of bleeding.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible.
• History or current diagnosis of any medical or psychological condition that in the Investigator's opinion, might interfere with the subject's ability to participate