GD2 CAR T Cell Therapy Achieves Long-Lasting Remissions in High-Risk Neuroblastoma Patients

A recent study from Bambino Gesù Children's Hospital in Rome has demonstrated that a third-generation CAR T cell therapy targeting GD2, known as GD2–CART01, can lead to sustained remissions and improved survival in children battling high-risk, metastatic, relapsed, or refractory neuroblastoma. Neuroblastoma, a common pediatric cancer, often has poor long-term outcomes after conventional treatments fail, with progression-free and overall survival rates typically below 20%. Although recent trials like the BEACON-Neuroblastoma trial and the Children's Oncology Group ANBL1221 have reported some improvements with chemoimmunotherapy approaches, response rates remain limited and relapse common.

The phase I/II trial, described in Nature Medicine, involved 32 children treated with GD2–CART01, a genetically engineered T cell therapy designed to target neuroblastoma cells expressing GD2. The trial aimed to evaluate safety, maximal tolerated dose, response rates, and long-term survival. Results showed a promising overall response rate of 66%, with complete remission observed in 37% of patients at six weeks, maintaining or increasing slightly over time. Notably, GD2–CART01 cells persisted for over a year in many recipients, correlating with longer-term remission.

Survival data was encouraging, with a median follow-up of 4.2 years and a five-year overall survival rate of approximately 43%. Patients with lower disease burden at treatment initiation had even better outcomes, with a five-year overall survival of nearly 68%. The therapy was associated with manageable side effects: cytokine release syndrome occurred mainly at grades 1–2, and neurotoxicity was controlled effectively using an inducible safety switch built into the CAR T cells.

Importantly, the study suggests that administering GD2–CART01 earlier in the disease course, particularly when disease burden is low, can significantly enhance treatment efficacy. The authors plan to expand this work with a multicenter international phase II trial. Overall, the findings highlight the potential for GD2-targeted CAR T cell therapy to transform treatment strategies for high-risk neuroblastoma, offering hope for durable remissions where conventional therapies have fallen short.