• Safety and tolerability of adjuvant personalized neoantigen DNA vaccine as measured by the number of grade 3 and 4 adverse events [ Time Frame: Through 30 days after completion of treatment (estimated to be 13 months) ]
• Feasibility of adjuvant personalized neoantigen DNA vaccine as measured the number of participants that had a neoantigen-specific DNA vaccine generated [ Time Frame: From time of resection to time of initiation (approximately 12-14 weeks) ]

• Safety and tolerability of adjuvant personalized neoantigen DNA vaccine as measured by the number of grade 3 and 4 adverse events [ Time Frame: Through 30 days after completion of treatment (estimated to be 13 months) ]
• Feasibility of adjuvant personalized neoantigen DNA vaccine as measured by the ability to identify and generate a neoantigen-specific DNA vaccine [ Time Frame: From time of resection to time of initiation (approximately 12-14 weeks) ]

• Median Progression Free Survival (PFS) [ Time Frame: 2 years ]
  • PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
  • Progressive Disease (PD): At least a 25% increase in the sum of products of perpendicular diameters of at least 1 target lesion, taking as reference the smallest sum of products of perpendicular diameters on study (this includes the baseline sum if that is the smallest on study). The absolute increase in any dimension must be at least 5mm when calculating the products of perpendicular diameters. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy* not caused by comorbid events.
• Median Overall Survival [ Time Frame: 2 years ]

• Biological: Personalized neoantigen DNA vaccine
  At each vaccination time point, patients will receive two injections of the neoantigen DNA vaccine, one injection into each deltoid or lateralis.
• Device: TDS-IM System
  The TDS-IM device utilizes the in vivo application of electrical fields to enhance the intracellular delivery of agents of interest in a targeted region of tissue
• Procedure: Peripheral blood draw
  -After trial enrollment and up to 7 days after the first vaccine dose (baseline); 2 weeks after last dose; time of progression or discontinuation (optional); other time points throughout the study if deemed pertinent to assessment of exploratory objectives (optional)

Inclusion Criteria:

• Any patient ≤ 39 years of age who was diagnosed with a pediatric brain tumor of any histologic subtype, who has now developed recurrent or refractory disease.
• Eligible to receive vaccine injections by TDS-IM electroporation device.
• Availability of tissue for sequencing to determine presence of targetable neoantigen. This may be fresh tissue collected as part of routine care, another research project or archived tissue from a previous craniotomy with biopsy, subtotal resection, total gross resection, or re-resection.
• Karnofsky/Lansky performance status ≥ 60%

Normal bone marrow and organ function as defined below:

• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)
• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN

• Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

  • Systemic corticosteroid therapy is permitted provided dosing is minimal based on age 0.1mg/kg/day with a max of 4mg daily (dexamethasone or equivalent) on the day of vaccine administration.
  • Bevacizumab will be allowed if given for symptomatic control of vasogenic edema and to avoid high dose of corticosteroids at the discretion of the treating physician.
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• As this is a safety and feasibility study, prior immunotherapy will be permitted. However, any prior immunotherapy must be discontinued at least 2 weeks before vaccine administration. Non-immunologic therapy may be continued.
• No candidate neoantigen identified during screening.
• A history of other malignancy ≤ 3 years previous with the exception of non-melanoma skin cancer, any in situ cancer that has been successfully resected and cured, treated superficial bladder cancer, or any early-stage solid tumor that was successfully resected without need for adjuvant radiation or chemotherapy.
• Currently receiving any other investigational agents.
• Known allergy, or history of serious adverse reaction to, vaccines such as anaphylaxis, hives, or respiratory difficulty.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• History of pre-existing immunodeficiency disorder, autoimmune condition requiring immunosuppressive therapy, or chronic infection (i.e. hepatitis B, hepatitis C, HIV). This includes inflammatory bowel disease, ulcerative colitis, Crohn's disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia, immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, sarcoidosis, or other rheumatologic disease or any other medical condition or use of medication which might make it difficult for the patient to complete the full course of treatments or to generate an immune response to vaccines.
• Presence of clinically significant increased intracranial pressure (e.g. impending herniation) or hemorrhage, uncontrolled seizures, or requirement for immediate palliative treatment.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of first dose of vaccine.
• Individuals in whom a skinfold measurement of the cutaneous and subcutaneous tissue for eligible injection sites (left and right medial deltoid region) exceeds 40 mm.
• Individuals in whom the ability to observe possible local reactions at the eligible injection sites (deltoid region) is, in the opinion of the investigator, unacceptably obscured due to a physical condition or permanent body art.
• Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region.
• Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, or hepatic or renal functional abnormality as determined by the investigator based on medical history, physical examination, EKG, and/or laboratory screening test.
• Any chronic or active neurologic disorder, including seizures and epilepsy, excluding a single febrile seizure as a child.
• Syncopal episode within 12 months of screening.
• Current use of any electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep brain stimulators.