Engineered Neuroblastoma Cellular Immunotherapy (ENCIT)-01

Upon meeting the eligibility requirements and enrolling on study, subjects will undergo
apheresis to obtain the T cells for the generation of the CD171 CAR+ T cells. The T cells are
isolated from the apheresis product, the CD4 and CD8 T cells are then selected and grown
separately, transduced with a lentivirus to express the CD171 CAR as well as a truncated EGFR
that has no signaling capacity (noted EGFRt) and expanded in culture over a 4-6 week period.
During the process of cell generation, subjects will continue to be cared for by their
primary oncologist and may undergo additional treatment directed at neuroblastoma during this
time.

After the CAR+ T cells have been generated, the subject undergoes a disease assessment and
determination of necessary lymphodepletion therapy. A variety of lymphodepletion strategies
are acceptable and determined on a case by case basis. At least 48 hours after the completion
of lymphodepletion, the subject will receive and infusion of CAR+ T cells at an approximate
1:1 ratio of CD4 to CD8 CAR+ T cells.

Following treatment with the CAR+ T cells, subjects will be followed intensely for 6 weeks
with serial blood testing and re-evaluation of disease status with MIBG scintigraphy, tumor
imaging by MRI/CT and bone marrow aspirates. After 4-6 weeks, the subjects clinical care will
be resumed by their primary oncologist, and it is possible that they would receive additional
chemotherapy or investigational agents.

Some subjects will receive cetuximab for ablation of the genetically modified T cells.
Criteria to receive cetuximab include acute toxicities that are life threatening, as well as
studies indicating lymphoproliferative disorder arising from an infused genetically modified
T cell.

Upon completion of the study, subjects will be followed bi-annually for 5 years, and then
annually for 10 additional years with either a medical history, physical exam and blood tests
or a phone call/questionnaire. This follow up will help to determine if the subject develops
any long-term health problems related to the CAR+ T cells including a new cancer.

Inclusion Criteria:

- Prior diagnosis of NB or ganglioneuroblastoma either by histologic verification and/or
demonstration of tumor cells in the bone marrow with increased catecholamine levels.

- Male or female subjects ≤ 26 years of age

- Diagnosis of high risk NB at initial diagnosis or if non-high risk at time of initial
diagnosis must have had evidence of metastatic progression when > 18 months of age.

- Measurable or evaluable disease

- Lansky or Karnofsky performance status score of ≥ 50

- Life expectancy of ≥ 8 weeks.

- Recovered from significant acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to enrollment onto this study.

- ≥ 7 days since last chemotherapy or biologic therapy administration

- No systemic corticosteroids (unless physiologic replacement dosing) within 7 days of
enrollment.

- ≥ 3 half-lives or 30 days from time of last dose of anti-tumor directed antibody
therapy, whichever is shorter from time of enrollment

- ≥ 6 weeks from myeloablative therapy and autologous stem cell transplant (timed from
stem cell infusion). Patients who received stem cell infusion following
non-myelo-ablative therapy are eligible once they meet all other eligibility
requirements. Patient must NOT have received a prior allogeneic hematopoietic stem
cell transplant.

- No prior genetically modified cell therapy that is still detectable or prior
virotherapy.

- Must not be receiving external beam radiation therapy at the time of study enrollment.
≥ 12 weeks from prior I131 MIBG therapy.

- Adequate organ function

- Adequate laboratory values

- Negative HIV antigen and antibody, Hepatitis B surface antigen and Hepatitis C
antibody within 3 months prior to enrollment. For patients with positive Hepatitis C
Ab, negative PCR testing must be documented in order to be eligible.

Exclusion Criteria:

- History of relevant CNS pathology or current relevant CNS pathology (non-febrile
seizure disorder requiring ongoing anti-epileptic medications, paresis, aphasia,
cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, cerebellar
disease, organic brain syndrome, psychosis, coordination or movement disorder).
Patients may have CNS intracranial tumor.

- Pregnant or breast-feeding

- Unable to tolerate apheresis procedure including placement of temporary apheresis
catheter if necessary

- Presence of active malignancy other than NB

- Presence of known intracranial metastatic neuroblastoma. Skull based disease with soft
tissue extension is allowed.

- Presence of active severe infection

- Presence of any concurrent medical condition that, in the opinion of the protocol PI
or designee, would prevent the patient from undergoing protocol-based therapy.

- Presence of a primary immunodeficiency/bone marrow failure syndrome

- Receiving any other anti-cancer agents or radiotherapy at the time of study entry

- Unwilling or unable to provide consent/assent for participation in the study and
15-year follow-up