Tissue Procurement Inclusion Criteria:

Patients will be eligible for tissue procurement for the Vigil manufacturing process, if they meet all of the following criteria:

• Histologically confirmed Ewing’s Sarcoma Family of Tumors (ESFT).
• Age ≥ 2 years.
• Estimated survival ≥ 6 months.
• Evidence of EWS translocation by FISH or RT-PCR or Next Generation Sequencing (NGS). If available, NGS sequencing report should be submitted to Gradalis.
• Recurrence or refractory to 1 line of systemic chemotherapy including but not limited to doxorubicin, vincristine and ifosfamide.
• Planned standard of care surgical procedure (e.g., tumor biopsy or palliative resection or thoracentesis) and expected availability of a cumulative soft-tissue mass of ~10-30 grams tissue ("grape" to "golf-ball" size / approximate 2 cm total diameter on imaging) and/or pleural fluid estimated volume ≥ 500mL (from a primary or secondary thoracentesis, yielding in a high volume of tumor cells) for immunotherapy manufacture.
• Tumor intended for immunotherapy manufacture is not embedded in bone and does not contain luminal tissue (e.g., bowel, ureter, bile duct).
• Ability to understand and the willingness to sign a written protocol specific informed consent for tissue harvest or a parental/guardian informed consent and pediatric assent when appropriate.

Tissue Procurement Exclusion Criteria:

Patients meeting any of the following criteria are not eligible for tissue procurement for the Vigil manufacturing:

• Medical condition requiring any form of chronic systemic immunosuppressive therapy (steroid or other) except physiologic replacement doses of hydrocortisone or equivalent (no more than 30 mg hydrocortisone or 10 mg prednisone equivalent daily) for < 30 days duration.
• Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 3 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected.
• Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months.
• Any documented history of autoimmune disease with exception of Type 1 diabetes on stable insulin regimen, hypothyroidism on stable dose of replacement thyroid medication, vitiligo, or asthma not requiring systemic steroids.
• Known HIV or chronic Hepatitis B or C infection.
• Known hypersensitivity to any temozolomide component or to dacarbazine (DTIC).
• Known hypersensitivity to irinotecan or its excipients.
• Known history of allergies or sensitivities to gentamicin.
• History of or current evidence of any condition (including medical, psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient’s participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.

Study Enrollment Inclusion Criteria:

Patients will be eligible for registration if they meet all of the following inclusion criteria:

• Completed manufacture of at least 4 vials of Vigil.
• Karnofsky performance status (KPS) / Lansky performance status (LS) ≥80%.
• Normal organ and marrow function as defined below:
  • Absolute granulocyte count ≥1,000/mm3;
  • Absolute lymphocyte count ≥400/mm3;
  • Platelets ≥75,000/mm3;
  • Hemoglobin ≥8.0 mg/dL;
  • Total bilirubin ≤ institutional upper limit of normal*;
  • AST(SGOT)/ALT(SGPT) ≤2x institutional upper limit of normal;
  • Creatinine <1.5 mg/dL.
  • *documented Gilbert’s syndrome may be considered after medical monitor review
• Subject has recovered to CTCAE Grade 1 (except for parameters noted in Item 3, above) or better from all adverse events associated with prior therapy or surgery. Pre-existing motor, sensory neurologic pathology or symptoms, or dermatologic must be recovered to CTCAE Grade 2 or better.
• If female of childbearing potential, has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a negative serum test will be required for study entry.
• Ability to understand and the willingness to sign a written informed protocol specific consent or a parental/guardian informed consent and pediatric assent when appropriate.

Study Enrollment Exclusion Criteria:

Measureable disease is not a requirement for enrollment onto the trial. In addition to the procurement exclusion criteria, patients will NOT be eligible for study registration and randomization if meeting any of the following criteria:

• Any anti-neoplastic therapy between tissue procurement for Vigil manufacture and start of study therapy.
• Live vaccine used for the prevention of infectious disease administered < 30 days prior to the start of study therapy.
• Post-surgery complication that in the opinion of the treating investigator would interfere with the patient’s study participation or make it not in the best interest of the patient to participate.