GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma

作者：Francesca Del Bufalo, Biagio De Angelis, Ignazio Caruana, Giada Del Baldo, Maria Antonietta De Ioris, Annalisa Serra, Angela Mastronuzzi, Maria Giuseppina Cefalo, Daria Pagliara, Matteo Amicucci, Giuseppina Li Pira, Giovanna Leone, Valentina Bertaina, Matilde Sinibaldi, Stefano Di Cecca, Marika Guercio, Zeinab Abbaszadeh, Laura Iaffaldano, Monica Gunetti, Stefano Iacovelli, Rossana Bugianesi, Stefania Macchia, Mattia Algeri, Pietro Merli, Federica Galaverna, Rachid Abbas, Maria Carmen Garganese, Maria Felicia Villani, Giovanna Stefania Colafati, F Bonetti, Marco Rabusin, Katia Perruccio, Veronica Folsi, Concetta Quintarelli, Franco Locatelli · 发表于：New England Journal of Medicine · 年份：2023 · DOI：10.1056/nejmoa2210859 · 被引用次数：563 · 研究领域：CAR-T cell therapy research、Neuroblastoma Research and Treatments、Virus-based gene therapy research

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. Download a PDF of the Research Summary. 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). 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%...