Identification of antigens specific for brain tumors

脑肿瘤特异性抗原的鉴定

• 批准号: 12557120
• 负责人: TODA Masahiro
• 金额: $ 8.51万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557120/
• 关键词: SEREX; gene; antigen; glioma; testis; serum; サイトカイン; グリオーマ抗原; ベクター

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.

中枢神经系统（CNS）一直被认为是一个免疫特权网站，然而，最近的证据表明，一系列的免疫事件可以启动时，免疫系统识别CNS抗原。为了开发一种新的针对胶质瘤的抗原特异性免疫治疗，我们尝试使用SEREX，通过重组表达克隆进行抗原的血清学鉴定来鉴定肿瘤抗原。用12例脑胶质瘤患者血清筛选脑胶质瘤细胞cDNA文库，共获得92个免疫反应性cDNA克隆，包含52个不同基因。然后，我们评估了这些抗原的识别神经胶质瘤患者，其他脑部疾病患者和正常人的血清。在52个不同的抗原筛选，我们确定了两个以前未表征的cDNA，KU-GB-1和KU-GB-2，其产品被识别的胶质瘤患者的血清。基因表达分析显示，KU-GB-1和KU-GB-2在胶质瘤中的表达高于正常组织（睾丸除外）。进一步用神经胶质瘤患者血清筛选睾丸cDNA文库，鉴定出三个以前未鉴定的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，并可作为诊断和治疗胶质瘤的靶点。

项目成果

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Suzuki,A：“HSV 和 IL-12 的多重原位癌症疫苗协同促进肿瘤消退。”Proc.Am.Assoc.Cancer Res.. 41. 469 (2000)

Toda,M.: "Combination Suicide/cytokine gene therapy as adjuvants to Defective Herpes Simplex Virus-Based Cancer Vaccine."Gene Ther. (in press). (2001)

Toda,M.：“联合自杀/细胞因子基因疗法作为有缺陷的单纯疱疹病毒癌症疫苗的佐剂。”Gene Ther。

Toda,M: "Expression of the Neural RNA-Binding Protein Musashil in Human Gliomas."Glia. (in press). (2001)

Toda，M：“神经 RNA 结合蛋白 Musashil 在人类神经胶质瘤中的表达。”神经胶质细胞。

Toda M, Iizuka Y, Kawase T, Uyemura K, Kawakami Y: "Immuno-viral therapy of brain tumors by combination of viral therapy with cancer vaccination using a replication-conditional HSV"Cancer Gene Ther. 9. 356-364 (2002)

Toda M、Iizuka Y、Kawase T、Uyemura K、Kawakami Y：“使用复制条件 HSV 将病毒疗法与癌症疫苗接种相结合，对脑肿瘤进行免疫病毒疗法”Cancer Gene Ther。

戸田正博, 戸山芳明: "樹状細胞"臨床整形外科. 37. 732-733 (2002)

Masahiro Toda，Yoshiaki Toyama：“树突状细胞”临床骨科 37. 732-733 (2002)。