Multi-antigen T Cell Infusion Against Neuro-oncologic Disease

Inclusion Criteria:

Recipient Procurement Inclusion Criteria

* Diagnosis of high-risk CNS tumors: DIPG, high-grade glioma, medulloblastoma, ependymoma, embryonal tumors, choroid plexus carcinoma, other aggressive CNS malignancies.

  o Group A (newly diagnosed DIPG): Radiographic diagnosis with DIPG defined as tumors with a pontine epicenter and diffuse intrinsic involvement of the pons. For Group A, procurement within the first 12 weeks after completion of radiotherapy is required.
  * Group B: Recurrent, progressive, or refractory disease after standard treatment. Refractory disease includes high-risk tumors with residual disease after completion of standard treatment or tumors with known poor cure rates with standard treatment.
* 6 months to 80 years of age at enrollment
* Karnofsky/Lansky score of ≥ 60%
* Organ function:

  o ANC greater than or equal to750/µL

  o Platelets greater than or equal to 75K

  o Bilirubin less than or equal to 1.5x ULN

  o AST/ALT less than or equal to 5x ULN

  o Serum creatinine less than or equal to 1.0mg/dL or 1.5x ULN for age (whichever is higher)
  * Pulse oximetry \> 90% on room air
* Agree to use contraceptive measures during study protocol participation (when age appropriate)
* Patient or parent/guardian capable of providing informed consent
* Available pre-trial tumor tissue (Optional for Group B patients, but highly encouraged. Also optional for Group A)
* Patient deemed to be of sufficient size in order to provide the necessary blood volume for TAA-T generation

Recipient Procurement Exclusion Criteria

* Patients with uncontrolled infections
* Patients with known HIV infection
* Pregnancy\*\* or lactating females
* Prior immunotherapy with an investigational agent within the last 28 days prior to procurement
* Patients with previous history of allogeneic stem cell transplantation (however, patients who have received autologous stem-cell infusions will remain eligible).
* Bulky tumor o Group B - patients who have bulky tumor on imaging are ineligible. These include the following: Tumor with any evidence of uncal herniation or significant midline shift Tumor with a significant brainstem component Patients who are deemed to have overly bulky tumor by the PI of the study

  * Pregnancy assessment on all patients \>7 years will be performed. If patient has child bearing potential (per PI/Sub-I discretion), then pregnancy testing will be performed.

Recipient Inclusion Criteria for Initial TAA-T Administration and for Subsequent Infusions

* Steroids \< 0.5 mg/kg/day dexamethasone or equivalent
* Karnofsky/Lansky score of greater than or equal to 60%
* Organ function:

  o ANC greater than or equal to750/µL

  o Platelets greater than or equal to 75K
  * Bilirubin less than or equal to 1.5x ULN
  * AST/ALT less than or equal to 5x ULN
  * Serum creatinine less than or equal 1.0mg/dL or 1.5x ULN for age (whichever is higher)
  * Pulse oximetry \> 90% on room air
* Patients must have received their last dose of known:

  o Myelosuppressive chemotherapy (including completing radiotherapy for group A patients): greater than or equal to14 days prior to TAA-T infusion or demonstrated count recovery

  o Investigational agent: 28 days prior to TAA-T infusion. For investigational agents that have known adverse events occurring beyond 28 days after administration, this period must be extended beyond the time when new adverse events are known to commonly occur.
  * Biologic agents: 7 days prior to TAA-T infusion. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time when new adverse events are known to commonly occur.
  * Bevacizumab: bevacizumab may be used if clinically indicated in order to control potential pseudoprogression\* or inflammation thought to be due to the cellular product. There will not be a standard required washout period for bevacizumab if used for this indication.
  * Surgery: patients must have recovered from all acute effects of prior surgical intervention
* Neurologic status: Patients with neurologic deficits must have deficits that are stable for a minimum of 7 days prior to TAA-T infusion

  * Pseudoprogression is a retrospective assessment that some (or all) noted tumor enlargement by radiographic criteria may reflect immune cell infiltration rather than true tumor progression. This diagnosis is commonly accepted to be retrospectively true if, in the context of clinical stability, radiographic progression plateaus when it would have been expected to progress.

Recipient Exclusion Criteria for Initial and Subsequent TAA-T Infusions

* Patients with uncontrolled infections
* Bulky tumor\*\*\* o Group B - patients who have bulky tumor on imaging are not eligible. These include the following: Tumor with evidence of uncal herniation or significant midline shift Tumor with a significant brainstem component Patients who are deemed to have overly bulky tumor by the PI of the study
* Patients who received ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of TAA-T cell infusion.

Pregnancy\*\* or lactating females

\*\* Pregnancy assessment on all patients \>7 years will be performed. If patient has child bearing potential (per PI/Sub-I discretion), then pregnancy testing will be performed.

\*\*\* For subsequent infusions, the most recent disease assessments (as obtained per standard of care) will be used to determine eligibility.