PHOX2B PC-CAR T Cells for Relapsed Neuroblastoma

Inclusion Criteria: 1. Patients must be ≥ 1 years of age 2. Patients must demonstrate expression of at least one of the following HLA alleles by HLA genotyping (conducted at CHOP) to be eligible: HLA-A\*24:02, HLA-A\*24:03, HLA-A\*24:04, HLA-A\*24:07, HLA-A\*24:124, HLA-A\*24:143, HLA-A\*24:17, HLA-A\*24:242, HLA-A\*24:305, HLA-A\*24:314, HLA-A\*24:33, HLA-A\*24:353, HLA-A\*24:41, HLA-A\*24:51, HLA-A\*24:63, HLA-A\*24:87, HLA-A\*24:92, HLA-A\*23:01, HLA-A\*23:17, HLA-A\*23:25, HLA-A\*23:39, 3. Disease Status A. Patients must have high-risk neuroblastoma according to COG risk classification at the time of study enrollment. Patients who were initially considered low- or intermediate-risk, but then reclassified as high-risk are also eligible. B. Patients must have a previously histologically confirmed diagnosis of neuroblastoma. C. Patients must have recurrent/progressive, refractory or persistent neuroblastoma. D. Patients must have neuroblastoma for which standard curative measures do not exist or are no longer effective. Note: Patients at first relapse are eligible as no known curative therapies exist for relapsed high-risk neuroblastoma. E. Patients must have evaluable or measurable disease at enrollment and at least one of the following: * Bone Sites a) MIBG avid tumors: 1. Patients with recurrent/progressive or refractory disease: a. At least 1 MIBG avid bone site. 2. Patients with persistent disease: 1. 3 or more MIBG avid sites (including soft tissue and/or bone). 2. 1 or 2 MIBG avid sites (including soft tissue and/or bone) with biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one MIBG avid site present at the time of enrollment. b) MIBG non-avid tumors: at least 1 bone lesion with either biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma at any time prior to enrollment OR both FDG-PET uptake AND MRI consistent with metastasis. * Bone marrow: Any amount of tumor cells in the bone marrow (including neuroblasts, mature and maturing ganglion cells). * Soft tissue site(s) a) At least one soft tissue lesion that meets criteria for a target lesion as defined by: 1. Size: Lesion can be accurately measured in at least one dimension with a longest diameter ≥ 10 mm or for discrete lymph nodes ≥ 15 mm short axis. 2\. In addition to size, a lesion needs to meet ONE of the following criteria: a. MIBG avid tumors: i. Patients with recurrent/progressive or refractory disease: 1\. At least one MIBG avid soft tissue site. ii. Patients with persistent disease: 1. 3 or more MIBG avid sites (including soft tissue and/or bone). 2. 1 or 2 MIBG avid sites (including soft tissue and/or bone), with biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one MIBG avid site present at the time of enrollment. b. MIBG non-avid tumors: biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma (with or without FDG uptake) in a soft tissue site present at time of enrollment OR both FDG-PET uptake AND MRI consistent with metastasis. b) At least one soft tissue lesion that does not meet size criteria for a target lesion but had a biopsy positive for neuroblastoma and/or ganglioneuroblastoma at any time prior to enrollment OR is in a patient with recurrent/progressive or refractory disease and is MIBG avid. 4\. Patients must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 60. 5\. Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN for age. 6\. Liver Function as follows: a. Total bilirubin ≤ 1.5 x ULN (exception: total bilirubin ≤ 3 ULN for patients with Gilbert's Disease or liver metastases). b. Alanine aminotransferase (ALT) ≤ 3.0 ULN (exception: ALT ≤ 5 x ULN for patients with liver metastases). c. Aspartate aminotransferase (AST) ≤ 3.0 ULN (exception: ALT ≤ 5 x ULN for patients with liver metastases). 7\. Pulmonary Function as follows: a. Patients need to have a baseline pulse oximetry of at least 92% on room air and DLCO ≥ 60% (corrected for anemia if necessary) if PFTs are clinically appropriate as determined by the treating investigator. 8\. Cardiac Function as follows: a. Left ventricular shortening fraction (LVSF) ≥28% or ejection fraction (LVEF) ≥ 50% confirmed by Echo, or adequate ventricular function documented by a scan or a cardiologist. 9\. Patients of child-bearing potential ( patients who have reached menarche and have not experienced treatment-related premature ovarian failure) must have a negative serum pregnancy test performed at the time of screening It is recommended that all patients of reproductive potential use at least one medically acceptable form of contraception for at least 1 year after their last infusion of PHOX2B PC-CAR T cells. Investigators shall counsel patients on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Exclusion Criteria: 1. Patients with active hepatitis B or active hepatitis C. 2. Patients with active HIV infection (patients undergoing anti-retroviral therapy with undetectable HIV viral load are eligible). 3. Patients with uncontrolled active infection. 4. Patients with primary or acquired immunodeficiency disorder. 5. Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well. 6. Patients with actively progressing CNS metastases, including parenchymal or leptomeningeal involvement. (Note: CNS imaging at screening is only required if there is a clinical indication of suspected CNS metastasis) 7. Active medical disorder that, in the opinion of the investigator, would substantially increase the risk of uncontrollable CRS and/or neurotoxicity. 8. Patients who have received any live vaccines within 30 days prior to enrollment. 9. Pregnant or nursing (lactating) patients.