Identification of antigens specific for brain tumors

中枢神经系统(CNS)一直被认为是免疫特异区；然而，最近的证据表明，当免疫系统识别CNS抗原时，可以启动一系列免疫学事件。为了开发一种新的针对胶质瘤的抗原特异性免疫疗法，我们尝试使用SEREX鉴定肿瘤抗原，通过重组表达克隆进行抗原的血清学鉴定。从12例脑胶质瘤患者血清中筛选出92个免疫反应阳性的cDNA克隆，共涉及52个不同的基因。然后，我们评估了来自胶质瘤患者、其他脑部疾病患者和正常人的血清对这些抗原的识别能力。在筛选的52个不同的抗原中，我们鉴定了两个以前没有特征的cDNA，KU-GB-1和KU-GB-2，它们的产物只被胶质瘤患者的血清识别。基因表达分析显示，KU-GB-1和KU-GB-2在胶质瘤组织中的表达水平均高于正常组织(睾丸除外)。通过对人脑胶质瘤患者血清的睾丸cDNA文库进行Serex进一步筛选，鉴定出三个以前未被鉴定的cDNA：KU-GB-3、KU-GB-4和KU-GB-5。这些结果表明，人脑胶质瘤中表达的蛋白质可以被患者的免疫系统识别，并可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.