The ganglioside antigen GD2 is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting
| Autor: | Jutta Meltzer, Jendrik Hardes, A. Luecke, Sibylle Pscherer, Silke Landmeier, Georg Gosheger, Bianca Altvater, Marc Hotfilder, C. Dierkes, Heribert Juergens, Sareetha Kailayangiri, K. Leuchte, U. Titze, Uta Dirksen, Claudia Rossig |
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| Rok vydání: | 2012 |
| Předmět: |
cancer targets
Adult Cytotoxicity Immunologic Male Cancer Research Adolescent Recombinant Fusion Proteins T-Lymphocytes Receptors Antigen T-Cell Immune Targeting Bone Neoplasms chemical and pharmacologic phenomena Mice SCID Sarcoma Ewing Biology Major histocompatibility complex cellular immunotherapy Granzymes Mice Young Adult Antigen Mice Inbred NOD Cell Line Tumor Gangliosides Spheroids Cellular medicine Animals Humans gene transfer Child Cell Proliferation Ganglioside GD2 biochemical phenomena metabolism and nutrition medicine.disease Coculture Techniques Oncology Antigens Surface Immunology biology.protein Female Sarcoma Translational Therapeutics Ewing sarcoma Neoplasm Transplantation Single-Chain Antibodies |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | 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 GD2 and led us to explore GD2 immune targeting in this cancer. Methods: We investigated GD2 expression in Ewing sarcoma by immunofluorescence staining. We then assessed the antitumour activity of T cells expressing a chimeric antigen receptor specific for GD2 against Ewing sarcoma in vitro and in vivo. Results: Surface GD2 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 GD2 expression. T cells specifically modified to express the GD2-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, GD2-specific cytolytic responses to allogeneic and autologous Ewing sarcoma, including tumour cells grown as multicellular, anchorage-independent spheres. GD2-specific T cells further had activity against Ewing sarcoma xenografts. Conclusion: GD2 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. |
| Databáze: | OpenAIRE |
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