Modified CAR T-Cell Therapy in the Treatment of Refractory and Relapsed Neuroblastoma

Children with refractory and relapsed neuroblastoma often have particularly poor outcomes and few options remaining for treating their disease. 

CAR T-cell therapy is an immunologic treatment that involves removing T cells (which are an important part of the body’s immune response system) from a patient, then modifying the T cell with an antigen receptor that specifically recognizes tumor cells. The modified T cells are then reinfused into the patient.

CAR T-cell therapy has shown great theoretical promise in a number of clinical trials. For patients with neuroblastoma, T cells are modified to recognize a molecule that is found on the surface of neuroblastoma cells but is not widely detected on normal cells.

However this target (GD2) is found on nerve cells, and there is a risk that treatment could be associated with pain for as long as the T cells persist in the body. To limit the risk of pain, researchers at the Children’s Center for Cancer Research led by Rochelle Bagatell, MD, are working to develop a transiently-modified T cell that limits the life of circulating modified T cells.

These T cells are modified with RNA, rather than DNA. RNA replication is finite, and the modified T cells will disintegrate over time rather than perpetuating indefinitely in the body.

A phase 1 trial is in place assessing dose range; three dose levels will be assessed for toxicity. Children who have undergone previous intensive therapy and are refractory to treatment or children who have relapsed are eligible to participate in the study. 

Once a dose with minimal toxicity has been established, work will continue to develop safe and effective permanently modified T cells as treatment for neuroblastoma.