Identification of antigens specific for brain tumors

中枢神经系统（CNS）一直被认为是一个免疫特权的部位；然而，最近的证据表明，当免疫系统识别中枢神经系统抗原时，可以启动一系列免疫事件。为了开发一种新的针对胶质瘤的抗原特异性免疫疗法，我们尝试用SEREX技术鉴定肿瘤抗原，用重组表达克隆技术鉴定抗原的血清学。从12例胶质瘤患者血清中筛选胶质瘤细胞系cDNA文库，共分离出92个免疫反应性cDNA克隆，其中包含52个不同的基因。然后我们评估了胶质瘤患者、其他脑部疾病患者和正常人血清对这些抗原的识别。在筛选的52种不同抗原中，我们鉴定了两种以前未被鉴定的cdna， KU-GB-1和KU-GB-2，其产物仅被胶质瘤患者的血清识别。基因表达分析显示，与除睾丸外的正常组织相比，KU-GB-1和KU-GB-2在胶质瘤中高表达。通过对胶质瘤患者血清的睾丸cDNA文库进行进一步的SEREX筛选，鉴定出三种以前未被鉴定的cDNA， KU-GB-3， KU-GB-4和KU-GB-5。这些结果表明，人胶质瘤中表达的蛋白可以被患者免疫系统识别，并可能作为胶质瘤诊断和治疗的靶点。

The central nervous system (CNS) has been considered to be an immunologically privileged site; however, recent evidence suggests that a series of immunological events can be initiated when the immune system recognizes CNS antigens. To develop a novel antigen-specific immunotherapy against glioma, we have attempted to identify tumor antigens using SEREX, serological identification of antigens by recombinant expression cloning. A total of 92 immunoreactive cDNA clones containing 52 different genes were isolated by screening of a cDNA library from glioma cell lines with 12 glioma patients' sera. We then evaluated the recognition of these antigens by sera from glioma patients, other brain disease patients, and normal individuals. Among 52 distinct antigens screened, we identified two previously uncharacterized cDNAs, KU-GB-1 and KU-GB-2, whose products were recognized only by sera from glioma patients. Gene expression analysis revealed that KU-GB-1 and KU-GB-2 were highly expressed in gliomas compared with normal tissues except testis. By further SEREX screening of a testis cDNA library with glioma patients' sera, three previously uncharacterized cDNAs, KU-GB-3, KU-GB-4, and KU-GB-5, were identified. These results indicate that proteins expressed in human glioma could be recognized by the immune system in the patients and may be utilized as targets for diagnosis and treatment of glioma.