AIM-2: A novel tumor antigen is expressed and presented by human glioma cells
AIM-2: A novel tumor antigen is expressed and presented by human glioma cells
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DOI：
10.1097/00002371-200405000-00006
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发表时间：
2004-05-01
影响因子：
3.9
通讯作者：
Ying, H
中科院分区：
文献类型：
--
作者：
Liu, GT;Yu, JS;Ying, H
(A)最近使用黑色素瘤反应性CD 8（+）T细胞鉴定了从（I）免疫选择（M）黑色素瘤-2（AIM-2）中分离的免疫原。AIM-2抗原在多种肿瘤类型中表达，包括神经外胚层肿瘤以及乳腺癌、卵巢癌和结肠癌。在这项研究中，我们分析了AIM-2在多形性胶质母细胞瘤（GBM）的原代培养细胞中的表达，并建立了GBM细胞系。我们发现，原代GBM细胞系分别表达88.4%和93.0%的非剪接和剪接的AIM-2。七个已建立的GBM细胞系中有五个表达非剪接和剪接的AIM-2。此外，对AIM-2肽（RSDSGQQARY）具有特异性的C9 CTL克隆以抗原特异性和HLA-A1限制性方式有效识别GBM肿瘤细胞。GBM肿瘤细胞的IFN-γ处理显著增加HLA-A1表达水平，并因此增加经处理的肿瘤细胞的CTL识别。更重要的是，我们的树突状细胞临床试验中的12名HLA-A1和AIM-2阳性患者中有7名在接种疫苗后在其PBMC中产生AIM-2特异性CTL活性。这些数据表明AIM-2可用作肿瘤抗原靶点，用于监测疫苗试验或开发针对神经胶质瘤患者的抗原特异性主动免疫疗法。
(A) under bar ntigen isolated from (I) under bar mmunoselected (M) under bar elanoma-2 (AIM-2) was recently identified using melanoma-reactive CD8(+) T cells. AIM-2 antigen is expressed in a wide variety of tumor types, including neuroectodermal tumors, as well as breast, ovarian and colon carcinomas. In this study, we analyzed AIM-2 expression in glioblastoma multiforme (GBM) in primary cultured cells and established GBM cell lines. We found that the primary GBM cell lines expressed 88.4% and 93.0% of non-spliced and spliced AIM-2, respectively. Five out of seven of the established GBM cell lines expressed both non-spliced and spliced AIM-2. Furthermore, the C9 CTL clone, which is specific for AIM-2 peptide (RSDSGQQARY), efficiently recognized GBM tumor cells in an antigen-specific and HLA-A1 restricted manner. IFN-gamma treatment of the GBM tumor cells dramatically increased HLA-A1 expression levels and, consequently, increased CTL recognition of the treated tumor cells. More importantly, seven out of 12 HLA-A1 and AIM-2 positive patients from our dendritic cell clinical trial generated AIM-2 specific CTL activity in their PBMC after vaccinations. These data indicate that AIM-2 could be used as a tumor antigen target for monitoring vaccine trials or to develop antigen specific active immunotherapy for glioma patients.