Background:~Patients with refractory and/or recurrent neuroblastoma have poor prognosis despite complex multimodal therapy; therefore, novel curative approaches are needed. The investigators are attempting to use T cells obtained directly from the patient, which can be genetically modified to express a 4th generation GD2-specific chimeric antigen receptor (4SCAR-GD2). The chimeric antigen receptor (CAR) molecules enable the T cells to recognize and kill neuroblastoma through the recognition of a surface antigen, GD2, which is expressed at high levels in neuroblastoma but not at significant levels on normal tissues. This study will evaluate the side effects and the best dose of a novel 4th generation anti-GD2 CAR T cells to refractory and/or recurrent neuroblastoma.~Objectives:~1. Primary: To determine the safety and feasibility of administration of 4SCAR-GD2 T cells to children with neuroblastoma following a cyclophosphamide/fludarabine preparative regimen.~2. Secondary:~To determine if the administration of 4SCAR-GD2 T cells can establish an antitumor effects in children with neuroblastoma who receive preparative regimen.~To describe the toxicity of administration of anti-GD2 CAR T cells in children with or without high-burden disease.~To evaluate the incidence and the treatment effect of cytokine release syndrome (CRS).~To determine the expansion and functional persistence of 4SCAR-GD2 T cells in the peripheral blood of patients and the correlation with antitumor effects.~Eligibility:~Patients 1-14 years of age, at least 10 kg, with neuroblastoma that has recurred after or not responded to standard therapy and is deemed incurable by standard therapy.~Design:~Participants will be screened through physical exam and medical history. Blood and urine samples will be collected. Imaging studies or bone marrow aspirates may be performed.~Peripheral blood mononuclear cells (PBMC) will be obtained by apheresis, and T cells will be activated and modified to express the 4SCAR-GD2 gene.~On Day -7, PBMC will be activated and enriched for T cells, which will be followed by 4SCAR-GD2 lentiviral transduction. The total culture time is approximately 5-10 days.~Participants will receive a preparative conditioning regimen comprising cyclophosphamide/fludarabine to prepare their immune system to accept the modified CAR T cells. The preparative regimen is consisted of fludarabine 25 mg/m(2) on days -4, -3 and -2 and cyclophosphamide 300 mg/m(2) on day-4, -3 and -2.~Participants will receive an infusion of the modified 4SCAR-GD2 T cells and closely followed up for treatment related responses.~Participants will have frequent follow-up visits to monitor the outcome of the treatment.
Patients with refractory and/or recurrent neuroblastoma have poor prognosis despite complex multimodel therapy and therefore, novel approaches are urgently needed. The investigators are attempt to treat this disease using T cells genetically modified with a 4th generation lentiviral chimeric antigen receptor (CAR) targeting GD2 (4SCAR-GD2). The 4SCAR-GD2-modified T cells can recognize and kill neuroblastoma through the recognition of GD2, a surface protein expressed at high levels on neuroblastoma but not on normal tissues. This study will evaluate the side effects and effective doses of 4SCAR-GD2 T cells in treating refractory and/or recurrent neuroblastoma.