Adoptive T Cell Therapy, DC Vaccines, and Hematopoietic Stem Cells Combined With Immune checkPOINT Blockade in Patients With Medulloblastoma

Eligibility Criteria

• 1. Children and young adults age 4-30 years with suspected recurrence/progression of Group 3 or 4 (non-SHH/non-WNT) MB since completion of definitive focal +/- craniospinal irradiation who are a candidate for surgical resection or biopsy. Of the 6 evaluable subjects, a minimum of 3 slots must be reserved for patients with confirmed Group 4 MB. Patients who are unable to receive radiation therapy due to genetic disorders that put them at significant risk for radiation-induced secondary malignancies (i.e. Gorlin's syndrome or NF1 mutation) are eligible for enrollment at first disease recurrence/progression.
• 2. Must be a candidate for surgery/biopsy Or tumor tissue obtained clinically, has been previously stored in a biorepository suitable for tumor RNA extraction and amplification and sample is made available to the PI.
• 3. Karnofsky or Lansky Performance Status (KPS) ≥ 60% (KPS for \> 16 years of age) or Lansky performance Score (LPS) of ≥ 60 (LPS for \< 16 years of age)
• 4. Adequate bone marrow and organ function as defined below:
• * ANC ≥ 1,000/mcL (unsupported)
• * Platelets ≥ 100,000/mcL (unsupported for at least 3 days)
• * Hemoglobin ≥ 9 g/dL (may be supported)
• * Serum creatinine ≤ 1.5 x IULN OR Creatinine clearance by Cockcroft-Gault ≥ 60 mL/min for patients with serum creatinine \> 1.5 x IULN
• * Serum total bilirubin ≤ 1.5 x IULN for age OR Direct bilirubin ≤ IULN for patients with total bilirubin \> 1.5 x IULN for age
• * AST (SGOT) and ALT (SGPT) ≤ 3 x IULN for age
• * Cardiac shortening fraction ≥27% or LVEF ≥50% by echocardiogram
• * Adequate pulmonary function defined as baseline pulse oximetry of ≥92% on room air
• 5. For females of childbearing potential, negative serum pregnancy test at enrollment
• 6. For women of childbearing potential (WOCBP) must be willing to use acceptable contraceptive methods to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug.
• 7. Signed informed consent by patient and/or legally authorized representative
• 1. Prior discontinuation of PD-1 inhibitor treatment due to toxicity or disease progression.
• 2. Corticosteroids equivalent to ≥ 4mg dexamethasone daily.
• 3. HIV, Hepatitis B, or Hepatitis C seropositive.
• 4. Known active infection or immunosuppressive disease.
• 5. Autoimmune disease requiring medical management with immunosuppressant.
• 6. Pregnancy or lactation, due to possible adverse effects on the developing fetus or infant.
• 7. Treatment with another investigational drug or other intervention within 30 days prior to projected first dose of study treatment (Priming phase with TTRNA-DC).
• 8. Severe, active co-morbidity, defined as follows:
• * Unstable angina and/or congestive heart failure requiring hospitalization.
• * Transmural myocardial infarction within the last 6 months.
• * Acute bacterial or fungal infection requiring intravenous antibiotics at time of enrollment.
• * Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy.
• * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
• * Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
• * Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy.