期刊
BRITISH JOURNAL OF CANCER
卷 106, 期 6, 页码 1123-1133出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2012.57
关键词
Ewing sarcoma; G(D2); cellular immunotherapy; gene transfer; cancer targets
类别
资金
- Deutsche Krebshilfe [109566]
- University of Muenster Faculty of Medicine 'Innovative Medizinische Forschung (IMF)'
- EU
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 zeta 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. British Journal of Cancer (2012) 106, 1123-1133. doi:10.1038/bjc.2012.57 www.bjcancer.com Published online 28 February 2012 (C) 2012 Cancer Research UK
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