Antitumor activity without on-target off-tumor toxicity of GD2-chimeric antigen receptor T cells in patients with neuroblastoma

Sci Transl Med. 2020 Nov 25;12(571):eabd6169. doi: 10.1126/scitranslmed.abd6169.


The reprogramming of a patient's immune system through genetic modification of the T cell compartment with chimeric antigen receptors (CARs) has led to durable remissions in chemotherapy-refractory B cell cancers. Targeting of solid cancers by CAR-T cells is dependent on their infiltration and expansion within the tumor microenvironment, and thus far, fewer clinical responses have been reported. Here, we report a phase 1 study (NCT02761915) in which we treated 12 children with relapsed/refractory neuroblastoma with escalating doses of second-generation GD2-directed CAR-T cells and increasing intensity of preparative lymphodepletion. Overall, no patients had objective clinical response at the evaluation point +28 days after CAR-T cell infusion using standard radiological response criteria. However, of the six patients receiving ≥108/meter2 CAR-T cells after fludarabine/cyclophosphamide conditioning, two experienced grade 2 to 3 cytokine release syndrome, and three demonstrated regression of soft tissue and bone marrow disease. This clinical activity was achieved without on-target off-tumor toxicity. Targeting neuroblastoma with GD2 CAR-T cells appears to be a valid and safe strategy but requires further modification to promote CAR-T cell longevity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Humans
  • Immunotherapy, Adoptive
  • Neoplasm Recurrence, Local
  • Neuroblastoma* / therapy
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Chimeric Antigen* / genetics
  • T-Lymphocytes
  • Tumor Microenvironment


  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen