The ganglioside antigen G D2 is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting
BRITISH JOURNAL OF CANCER(2012)
Abstract
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-28 ζ 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.
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Key words
Ewing sarcoma,GD2,cellular immunotherapy,gene transfer,cancer targets
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