The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting.
The ganglioside antigen G(D2) is surface-expressed in Ewing sarcoma and allows for MHC-independent immune targeting.
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DOI：
10.1038/bjc.2012.57
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发表时间：
2012-03-13
影响因子：
8.8
通讯作者：
Rossig, C.
中科院分区：
文献类型：
--
作者：
Kailayangiri, S.;Altvater, B.;Meltzer, J.;Pscherer, S.;Luecke, A.;Dierkes, C.;Titze, U.;Leuchte, K.;Landmeier, S.;Hotfilder, M.;Dirksen, U.;Hardes, J.;Gosheger, G.;Juergens, H.;Rossig, C.
播散性尤文氏肉瘤需要新的治疗策略。原始神经外胚层特征和间充质干细胞起源都与神经节苷抗原GD2的异常表达相容，并引导我们探索GD2在该癌症中的免疫靶向。采用免疫荧光染色法检测GD2在Ewing肉瘤中的表达。然后，我们在体外和体内评估了表达GD2特异性嵌合抗原受体的T细胞抗尤文氏肉瘤的抗肿瘤活性。在10个Ewing肉瘤细胞系中的10个和3个原代细胞培养中检测到表面GD2。此外，14例患者中有12例的诊断活检显示GD2表达一致。特异性修饰表达gd2特异性嵌合受体的T细胞G2a-28ζ有效地与尤文氏肉瘤细胞相互作用，导致抗原特异性的细胞因子分泌。此外，来自健康供体和患者的嵌合受体基因修饰的T细胞对异体和自体尤文氏肉瘤（包括作为多细胞、不依赖锚定球体生长的肿瘤细胞）发挥了有效的gd2特异性细胞溶解反应。gd2特异性T细胞进一步具有抗异种移植尤文氏肉瘤的活性。GD2表面表达是尤文氏肉瘤的一个特征，为免疫治疗策略根除微转移细胞和预防高危疾病复发提供了合适的靶抗原。
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. 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. 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. 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.
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影响因子：
56.9
作者：
Morgan, Richard A.;Dudley, Mark E.;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
DOI：
10.1158/1078-0432.ccr-10-0735
发表时间：
2010-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cho D;Shook DR;Shimasaki N;Chang YH;Fujisaki H;Campana D
通讯作者：
Campana D
病毒特异性的T细胞设计为共表达肿瘤特异性受体：神经母细胞瘤个体中的持久性和抗肿瘤活性。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
20.3
作者：
Martinez, Caridad;Hofmann, Ted J.;Horwitz, Edwin M.
通讯作者：
Horwitz, Edwin M.
影响因子：
45.3
作者：
Ladenstein, Ruth;Poetschger, Ulrike;Juergens, Heribert
通讯作者：
Juergens, Heribert