GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma

N Engl J Med. 2023 Apr 6;388(14):1284-1295. doi: 10.1056/NEJMoa2210859.


Background: Immunotherapy with chimeric antigen receptor (CAR)-expressing T cells that target the disialoganglioside GD2 expressed on tumor cells may be a therapeutic option for patients with high-risk neuroblastoma.

Methods: In an academic, phase 1-2 clinical trial, we enrolled patients (1 to 25 years of age) with relapsed or refractory, high-risk neuroblastoma in order to test autologous, third-generation GD2-CAR T cells expressing the inducible caspase 9 suicide gene (GD2-CART01).

Results: A total of 27 children with heavily pretreated neuroblastoma (12 with refractory disease, 14 with relapsed disease, and 1 with a complete response at the end of first-line therapy) were enrolled and received GD2-CART01. No failure to generate GD2-CART01 was observed. Three dose levels were tested (3-, 6-, and 10×106 CAR-positive T cells per kilogram of body weight) in the phase 1 portion of the trial, and no dose-limiting toxic effects were recorded; the recommended dose for the phase 2 portion of the trial was 10×106 CAR-positive T cells per kilogram. Cytokine release syndrome occurred in 20 of 27 patients (74%) and was mild in 19 of 20 (95%). In 1 patient, the suicide gene was activated, with rapid elimination of GD2-CART01. GD2-targeted CAR T cells expanded in vivo and were detectable in peripheral blood in 26 of 27 patients up to 30 months after infusion (median persistence, 3 months; range, 1 to 30). Seventeen children had a response to the treatment (overall response, 63%); 9 patients had a complete response, and 8 had a partial response. Among the patients who received the recommended dose, the 3-year overall survival and event-free survival were 60% and 36%, respectively.

Conclusions: The use of GD2-CART01 was feasible and safe in treating high-risk neuroblastoma. Treatment-related toxic effects developed, and the activation of the suicide gene controlled side effects. GD2-CART01 may have a sustained antitumor effect. (Funded by the Italian Medicines Agency and others; number, NCT03373097.).

MeSH terms

  • Caspase 9 / adverse effects
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Caspase 9 / therapeutic use
  • Child
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Immunotherapy, Adoptive* / methods
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / therapy
  • Neuroblastoma* / genetics
  • Neuroblastoma* / therapy
  • Receptors, Chimeric Antigen* / therapeutic use


  • Caspase 9
  • ganglioside, GD2
  • Receptors, Chimeric Antigen

Associated data