The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting

Br J Cancer. 2012 Mar 13;106(6):1123-33. doi: 10.1038/bjc.2012.57. Epub 2012 Feb 28.


Background: Novel treatment strategies are needed to cure disseminated Ewing sarcoma. Primitive neuroectodermal features and a mesenchymal stem cell origin are both compatible with aberrant expression of the ganglioside antigen G(D2) and led us to explore G(D2) immune targeting in this cancer.

Methods: We investigated G(D2) expression in Ewing sarcoma by immunofluorescence staining. We then assessed the antitumour activity of T cells expressing a chimeric antigen receptor specific for G(D2) against Ewing sarcoma in vitro and in vivo.

Results: Surface G(D2) was detected in 10 out of 10 Ewing sarcoma cell lines and 3 out of 3 primary cell cultures. Moreover, diagnostic biopsies from 12 of 14 patients had uniform G(D2) expression. T cells specifically modified to express the G(D2)-specific chimeric receptor 14. G2a-28ζ efficiently interacted with Ewing sarcoma cells, resulting in antigen-specific secretion of cytokines. Moreover, chimeric receptor gene-modified T cells from healthy donors and from a patient exerted potent, G(D2)-specific cytolytic responses to allogeneic and autologous Ewing sarcoma, including tumour cells grown as multicellular, anchorage-independent spheres. G(D2)-specific T cells further had activity against Ewing sarcoma xenografts.

Conclusion: G(D2) surface expression is a characteristic of Ewing sarcomas and provides a suitable target antigen for immunotherapeutic strategies to eradicate micrometastatic cells and prevent relapse in high-risk disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antigens, Surface / immunology
  • Antigens, Surface / metabolism
  • Bone Neoplasms / immunology
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / therapy
  • Cell Line, Tumor
  • Cell Proliferation
  • Child
  • Coculture Techniques
  • Cytotoxicity, Immunologic
  • Female
  • Gangliosides / immunology
  • Gangliosides / metabolism*
  • Granzymes / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasm Transplantation
  • Receptors, Antigen, T-Cell / biosynthesis
  • Receptors, Antigen, T-Cell / metabolism
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / metabolism
  • Sarcoma, Ewing / immunology
  • Sarcoma, Ewing / metabolism*
  • Sarcoma, Ewing / therapy
  • Single-Chain Antibodies / biosynthesis
  • Single-Chain Antibodies / metabolism
  • Spheroids, Cellular / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / transplantation*
  • Young Adult


  • Antigens, Surface
  • Gangliosides
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • Single-Chain Antibodies
  • ganglioside, GD2
  • Granzymes