Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma

Blood. 2011 Dec 1;118(23):6050-6. doi: 10.1182/blood-2011-05-354449. Epub 2011 Oct 7.


We generated MHC-independent chimeric antigen receptors (CARs) directed to the GD2 antigen expressed by neuroblastoma tumor cells and treated patients with this disease. Two distinguishable forms of this CAR were expressed in EBV-specific cytotoxic T lymphocytes (EBV-CTLs) and activated T cells (ATCs). We have previously shown that EBV-CTLs expressing GD2-CARs (CAR-CTLs) circulated at higher levels than GD2-CAR ATCs (CAR-ATCs) early after infusion, but by 6 weeks, both subsets became low or undetectable. We now report the long-term clinical and immunologic consequences of infusions in 19 patients with high-risk neuroblastoma: 8 in remission at infusion and 11 with active disease. Three of 11 patients with active disease achieved complete remission, and persistence of either CAR-ATCs or CAR-CTLs beyond 6 weeks was associated with superior clinical outcome. We observed persistence for up to 192 weeks for CAR-ATCs and 96 weeks for CAR-CTLs, and duration of persistence was highly concordant with the percentage of CD4(+) cells and central memory cells (CD45RO(+)CD62L(+)) in the infused product. In conclusion, GD2-CAR T cells can induce complete tumor responses in patients with active neuroblastoma; these CAR T cells may have extended, low-level persistence in patients, and such persistence was associated with longer survival. This study is registered at as #NCT00085930.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adoptive Transfer / methods*
  • Antigens, Tumor-Associated, Carbohydrate / immunology
  • Bone Marrow Neoplasms / genetics
  • Bone Marrow Neoplasms / immunology
  • Bone Marrow Neoplasms / therapy
  • Bone Neoplasms / genetics
  • Bone Neoplasms / immunology
  • Bone Neoplasms / therapy*
  • Cell Line, Tumor
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Gangliosides / immunology*
  • Genetic Therapy / methods*
  • Humans
  • Immunologic Memory / immunology
  • Male
  • Neoplasm, Residual / genetics
  • Neoplasm, Residual / immunology
  • Neoplasm, Residual / therapy
  • Neuroblastoma / genetics
  • Neuroblastoma / immunology
  • Neuroblastoma / therapy*
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / immunology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Young Adult


  • Antigens, Tumor-Associated, Carbohydrate
  • Gangliosides
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • ganglioside, GD2

Associated data