EBV-specific CTLs for Neuroblastoma
(NESTLES Trial)
Trial Summary
What is the purpose of this trial?
Patients have high-risk neuroblastoma, a form of cancer typically found in children. The patients previously participated in a gene transfer research study using special immune cells. This research study combines two different ways of fighting disease, antibodies and T cells. Antibodies are types of proteins that protect the body from bacterial and other infections. T cells, also called cytotoxic T lymphocytes or CTLs, are special infection-fighting blood cells that can kill some tumor cells. Both antibodies and T cells have been used to treat patients with cancers and while they have shown promise, they have not been strong enough to cure most patients. The antibody used in this study is called 14g2a. This antibody sticks to neuroblastoma cells because of a substance on the outside of these cells called GD2. 14g2a and other antibodies that bind to GD2 have been used to treat people with neuroblastoma. For this study 14g2a has been changed so that instead of floating free in the blood, it is now joined to T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. T lymphocytes or CTLs can kill tumor cells but there normally are not enough of them to kill all tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the patient. Sometimes an antibody or chimeric receptor is attached to these T cells to help them bind to tumor cells. These chimeric receptor-T cells seem to kill some of the tumor, but they don't last very long in the body and so the tumor eventually comes back. We have found that T cells that are also trained to recognize the virus that causes infectious mononucleosis, Epstein Barr Virus (EBV), can stay in the blood stream for many years. By joining the 14g2a antibody to the CTLs that recognize EBV, we believe we will make a cell that can last a long time in the body (because they are EBV-specific) and recognize and kill neuroblastoma cells (because an antibody that can recognize these cells has been placed on their surface). Patients received treatment with the immune cells described above. They may want to receive an additional dose of these cells. This is being offered as an option because their neuroblastoma has returned and they have enough cells remaining to provide the patients with an additional dose. These 14g2a antibody CTLs are an investigational product not approved by the Food and Drug Administration.
Will I have to stop taking my current medications?
The trial protocol does not specify whether you need to stop taking your current medications. However, you must not be receiving any investigational agents or have received any tumor vaccines within the previous 6 weeks.
What data supports the effectiveness of the treatment EBV-specific CTLs for Neuroblastoma?
Research shows that GD2-directed chimeric antigen receptor (CAR) T cells, which are part of the treatment, helped shrink tumors in children with neuroblastoma. Additionally, EBV-specific CTLs expressing a GD2-specific receptor survived longer and were associated with tumor regression in some patients.12345
Is the treatment with EBV-specific CTLs for neuroblastoma safe?
Research shows that using EBV-specific CTLs for neuroblastoma appears to be safe, with some patients experiencing tumor regression or necrosis. In early clinical trials, CAR T cell therapy, which includes EBV-specific CTLs, has been found to be safe and feasible, although challenges remain in improving its effectiveness.12367
How is the EBV-specific CTLs treatment for neuroblastoma different from other treatments?
This treatment is unique because it uses genetically engineered T cells that target both the Epstein-Barr virus (EBV) and the GD2 antigen on neuroblastoma cells, enhancing their survival and antitumor activity compared to other T cells. This dual targeting approach allows the modified T cells to persist longer in the body, potentially leading to better outcomes in shrinking tumors.13458
Research Team
Andras A Heczey, MD
Principal Investigator
Baylor College of Medicine
Eligibility Criteria
This trial is for children with high-risk neuroblastoma who have relapsed or persistent disease after initial therapy. They must not require oxygen (>90% on room air), expect to live at least 12 weeks, and recovered from previous chemotherapy effects. No investigational agents or tumor vaccines should have been received in the last 6 weeks. Participants need normal blood counts, liver and kidney function, no severe heart/lung issues, a decent performance score (Karnofsky/Lansky >60%), and specific immune cells from a prior study.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive escalating doses of 14g2a.zeta chimeric receptor transduced autologous EBV specific cytotoxic T-lymphocytes and 14g2a.zeta transduced autologous peripheral blood T-cells
Follow-up
Participants are monitored for safety and effectiveness after treatment, including long-term monitoring for gene transfer side effects
Optional Additional Dose
Participants may receive an additional dose of cells if desired due to neuroblastoma recurrence
Treatment Details
Interventions
- EBV Specific CTLs
- GD-2 Specific Chimeric T Cell Receptors
Find a Clinic Near You
Who Is Running the Clinical Trial?
Baylor College of Medicine
Lead Sponsor
Center for Cell and Gene Therapy, Baylor College of Medicine
Collaborator