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Malignant mesothelioma associated antigens recognized by tumor infiltrating B cells. -usefulness of antibody titer to the antigens -

肿瘤浸润 B 细胞识别恶性间皮瘤相关抗原。

基本信息

批准号：
18591570
负责人：
HANAGIRI Takeshi
金额：
$ 2.44万
依托单位：
University of Occupational and Environmental Health, Japan
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591570/
关键词：
Malignant pleural mesothelioma tumor antigen antibody SEREX

项目摘要

Malignant pleural mesothelioma is difficult to be diagnosed at early stage and universally accepted therapy has not been established. In this study, we tried to obtain tumor specific antibody derived from tumor infiltrated B lymphocytes (TIB) in malignant mesothelioma by using xenotransplanted SCID mice model, and applied TIB-produced IgG to serological identification of antigens by recombinant expression cloning method (SEREX).Surgical specimens from 5 patients with malignant mesothelioma have been tried to establish tumor cell lines, and also these mesothelioma tissues were engrafted subcutaneously in SCID mice and blood samples were obtained every 2 weeks after xenotransplantation. Two mesothelioma cell lines have been established (K921MS0 and L324MSO). cDNA library was constructed from a tumor cell line (K921MS0) of malignant mesothelioma. Immunoscreening of the library was performed using the serum from SCID mice transplanted with mesothelioma tissues. Immuno-reactive cDNA clones … More were subcloned, and analyzed using database for homology search. Antibodies titers against the identified antigens were analyzed in sera of patients with malignant mesothelioma.Immunohistochemical staining revealed that B lymphocytes infiltrated in tumor tissues. In all SCID mouse serum, human IgG antibody could be detected (ranged from 134 to 24000μg/ml). By using antibodies derived from TIB, 11 antigens were identified. Six antigens showed over expression for malignant mesothelioma. Antibodies against the 6 antigens could be detected not only in serum of SCID mouse but also in sera of mesothelioma patients. Among them, antibody against Gene-X was detected in 7 out of 12 mesothelioma patients, and antibody against Thrombospondin-2 was detected in 11 out of 12 mesothelioma patients.Our results suggest that the B cells infiltrated in the tumor tissues have been sensitized and produced antibody against tumor associate antigens. Among the SEREX defined antigens, 2 antigens (Gene-X and Thrombosponddin-2) were overexpressed in malignant mesothelioma, and antibodies against them could be detected in higher proportion of mesothelioma patients than normal healthy persons. These two antigens could be used as tumor markers for diagnosis of patients with malignant mesothelioma. Less

恶性胸膜间皮瘤早期诊断困难，治疗方法尚未确立。本研究利用SCID小鼠移植瘤模型，从恶性间皮瘤中肿瘤浸润的B淋巴细胞（TIB B lymphocyte，TIB）中提取肿瘤特异性抗体，应用重组表达克隆法（SEREX）进行抗原的血清学鉴定。并将这些间皮瘤组织皮下移植到SCID小鼠中，异种移植后每2周采集血样。已经建立了两种间皮瘤细胞系（K921 MS 0和L324 MSO）。从恶性间皮瘤肿瘤细胞系（K921 MS 0）构建了cDNA文库。使用来自移植有间皮瘤组织的SCID小鼠的血清进行文库的免疫筛选。免疫反应性cDNA克隆 ...更多信息亚克隆，并使用数据库进行同源性搜索。恶性间皮瘤患者血清中抗所鉴定抗原的抗体滴度分析，免疫组化染色显示肿瘤组织中有B淋巴细胞浸润。在所有SCID小鼠血清中均能检测到人IgG抗体（范围为134 ~ 24000μg/ml）。通过使用TIB衍生的抗体，鉴定了11种抗原。恶性间皮瘤中有6种抗原呈过表达。这6种抗原的抗体不仅在SCID小鼠血清中检测到，而且在间皮瘤患者血清中也检测到。其中7例检测到Gene-X抗体，11例检测到Thrombospondin-2抗体，提示肿瘤组织中浸润的B细胞已被致敏并产生抗肿瘤相关抗原的抗体。在SEREX定义的抗原中，2种抗原（Gene-X和Thrombosponddin-2）在恶性间皮瘤中过表达，并且在间皮瘤患者中可以检测到针对它们的抗体的比例高于正常健康人。这两种抗原可作为诊断恶性间皮瘤的肿瘤标志物。少