To make the T cells, the investigators will take patient's blood and stimulate it with growth factors that make T cells grow. Investigators will use a retrovirus to insert the GD2-targeting chimeric antigen receptor (CAR) into the T cells. To make NK cells, investigators will take blood from healthy donors and stimulate them with growth factors that make NK cells grow. Investigators will also use a retrovirus to insert the tumor environment-targeting NK receptor, called NKG2D.zeta, into the NK cells.
The cells generated will be frozen and stored to give back to the patient. Because patients will have received cells with a new gene in them, patients will be followed for a total of 15 years to see if there are any long term side effects of gene transfer.
Patients will be assigned a dose of i15.NKG2D.zeta-NK cells. The assigned dose of cells is based on body weight and height.
In this study, patients will receive the i15.NKG2D.zeta-NK and C7R.GD2.CAR-T cells. On Day -5, the patient will be given an injection of i15.NKG2D.zeta-NK cells into the vein through an IV line at the assigned dose. Before receiving the NK cell infusion, the patient may be given a dose of Benadryl (diphenhydramine) and Tylenol (acetaminophen). The infusion will take between 1 to 10 minutes. Investigators will then monitor the patient in the clinic for about 3 hours. The study was designed to not give doses of lymphodepletion chemotherapy prior to the i15.NKG2D.zeta-NK and C7R.GD2.CAR-T cells. However, some patients may need to receive lymphodepletion chemotherapy prior to the NK cell infusion, based on preliminary study results.
This will be followed by an injection of C7R.GD2.CAR-T cells on Day 0. Before receiving the infusion, the patient may be given doses of Benadryl (diphenhydramine) and Tylenol (acetaminophen). The infusion will take between 1 to 10 minutes. Investigators will monitor the patient in the clinic for about 3 hours. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital. The patient may need to stay in Houston for up to 4 weeks after the infusion so we can monitor for side effects.
The patient will have follow-up visits after the T cell infusion at day -3, day +3, weeks 1, 2, 3, 4, and 8, then at months 3, 6, 9, an d 12, and then twice a year for the next 4 years and annually for the next 10 years. The patient will also have scheduled disease evaluations after the T cell injection at week 6 and then as clinically needed.
Medical test before treatment--
Before being treated, the patient will receive a series of standard medical tests:
* Physical exam
* Blood tests to measure blood cells, kidney and liver function
* Measurements of the tumor by routine imaging studies and/or bone marrow evaluation. We will use the imaging studies that have been used in the past to best assess the tumor: Computed Tomography (CT) scan, Magnetic Resonance Imaging (MRI), Position Emission Tomography (PET/CT), Bone Scan, and/or MIBG scan.
* Pulmonary Function Tests (PFT) to see how well the patient's lungs are working.
Medical tests during and after treatment--
The patient will receive standard medical tests when they are getting the infusions and afterwards:
* Physical exams
* Blood tests to measure blood cells, kidney and liver function
* Measurements of the tumor by routine imaging studies and/or bone marrow evaluation 6 weeks after the infusion (if the bone marrow showed tumor before the infusion).
To learn more about the way the i15.NKG2D.zeta-NK cells and C7R.GD2.CAR-T cells are working and how long they last in the body, an extra amount of blood will be obtained on the day of the NK-cell infusion and the T-cell infusion and at the end of the NK-cell and T-cell infusions, 1, 2, 3, 4, and 8 weeks after the T-cell infusion and every 3 months for the 1st year, every 6 months for the next 4 years and annually for the next 10 years. The amount of blood taken will be based on the patient's weight with up to a maximum of 60 mL (12 teaspoons) of blood to be obtained at any one time. For children, the total amount of blood drawn will not be more than 3 mL (less than 1 teaspoon) per 1 kg of body weight on any one day. This volume is considered safe, but may be decreased if patient is anemic (has a low red blood cell count).
During the time points listed above, if the i15.NKG2D.zeta-NK cells or C7R.GD2.CAR-T cells are found in the patient's blood at a certain amount, an extra 5 mL (about 1 teaspoon) of blood may need to be collected for additional testing.
If the patient has a procedure where tumor samples are obtained, like a repeat bone marrow evaluation or tumor biopsy, the investigators will request a sample to be used for research purposes.
The patient will receive supportive care for any acute or chronic toxicities, including blood components or antibiotics, and other intervention as medically appropriate.
