CAR-T Therapy: A Lifesaving Treatment for Children with Deadly Nervous System Tumors

An Innovative Therapy Shows Early Promise in Fighting Rare and Aggressive Childhood Cancer by Enhancing Immune System to Target Tumor Cells. Experts Remain Cautiously Optimistic, Emphasizing the Need for Larger Studies to Determine Treatment Efficacy and Role in Battling Neuroblastoma.

Neuroblastoma, a type of cancer that develops in undeveloped nerve cells, typically manifests in the abdomen and mostly impacts infants and young children under the age of 5. The American Cancer Society reports that approximately 800 children are diagnosed with the illness in the United States annually. Alarmingly, nearly half of these children are classified as “high risk” due to late detection of the cancer after it has metastasized.

Once diagnosed as “high risk,” a child requires an intense treatment plan. The conventional approach involves administering high-dose chemotherapy, conducting surgery to remove any remaining visible tumors, administering further chemotherapy, performing a stem cell transplant to rejuvenate the immune system, and lastly, radiation therapy.

A novel therapy has been added to the conventional treatment plan in recent years – the monoclonal antibody drug dinutuximab. This drug targets GD2, a protein present on the surface of numerous neuroblastoma cells. The drug is administered in combination with specific immune system proteins to stimulate the child’s immune response against the cancer cells that survived the previous treatment.

Unfortunately, despite the intensive treatment regimen, a considerable number of children continue to succumb to the disease. As per the researchers of the new study conducted at Bambino Gesù Children’s Hospital in Rome, approximately 40% to 50% of children survive without recurrence even after five years. The study findings were published on April 6 in the New England Journal of Medicine.

A recent study involved 27 children who were diagnosed with highly challenging cases of high-risk neuroblastoma, where either the cancer had relapsed or was unresponsive to initial treatments. Nearly half of the children had already undergone treatment with dinutuximab. In an attempt to treat these cases, the researchers utilized CAR T-cell therapy – a treatment tactic that has exhibited significant success in some cases of aggressive blood cancers but is not yet proven for treating other forms of cancer.

CAR T-cell therapy, akin to dinutuximab, also engages the immune system, albeit through a distinct approach. In this treatment, a patient’s T cells are extracted and genetically modified to include chimeric antigen receptors (CARs) to specifically recognize particular markers present on the surface of cancerous cells. The modified T cells are then reintroduced into the patient’s body, where they can effectively target and attack the cancer cells.

The T cells used in this trial were designed to detect and target the GD2 protein present in neuroblastoma. Within six weeks of treatment, the disease partially regressed in 63% of the children who underwent the therapy. Notably, one-third of the children showed no evidence of the disease, although four of them eventually experienced a relapse.

After three years, 40% of all children participating in the trial survived, but the survival rate was higher (60%) in the subset of children receiving the highest dose of CAR T-cell therapy.

Dr. Rani George, a pediatric hematologist/oncologist at Boston Children’s Hospital/Dana-Farber Cancer Institute, commented on the results, stating that they appear encouraging. However, given that this was a small-scale study with only a three-year follow-up period, further and more extensive clinical trials are necessary before CAR T-cell therapy can be considered a widely-accepted treatment option for neuroblastoma. Dr. George was not involved in the trial.

Dr. George pointed out that it remains unclear whether CAR T-cell therapy could be more efficacious than the current standard treatment involving dinutuximab. She suggested that CAR T cells could potentially prevent certain side effects of the antibody, such as pain. Alternatively, CAR T-cell therapy could be a viable alternative for children who do not respond to dinutuximab.

Dr. George cautioned that the potential benefits and risks of CAR T-cell therapy for neuroblastoma are still uncertain. While it can be an effective treatment, CAR T cells may also cause significant side effects, including cytokine release syndrome. This occurs when the T cells release large amounts of cytokines into the bloodstream, causing symptoms such as high fever and sudden drops in blood pressure, which can be fatal in severe cases.

Dr. George pointed out that in the trial, the majority of the children experienced cytokine release syndrome, but their cases were mild. To ensure safety, the Italian researchers included an “off switch” in the CAR T cells. This off switch, when activated by medication, triggers the T cells to self-destruct and potentially prevent severe side effects.

According to Drs. Oladapo Yeku and Dan Longo, of Massachusetts General Hospital Cancer Center and Harvard Medical School, in theory, the “off switch” gene incorporated into the CAR T cells could help manage severe cases of cytokine release syndrome.

An editorial published with the study by Drs. Oladapo Yeku and Dan Longo of Massachusetts General Hospital Cancer Center and Harvard Medical School, highlights the safety and efficacy of the therapy as “favorable.” However, they also emphasize the need for larger studies and understanding why some children with neuroblastoma respond to CAR T cells while others do not.

Source: HealthDay