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Isolation of human tumor antigens recognized by antibodies for development of immunotherapy and gene therapy

分离抗体识别的人类肿瘤抗原，用于开发免疫疗法和基因疗法

基本信息

批准号：
10470264
负责人：
KAWAKAMI Yutaka
金额：
$ 8.38万
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：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470264/
关键词：
Tumor antigens SEREX Antibody T cells Pancreatic cancer Esophageal cancer Colon cancer Melanoma 悪性黒色腫固形癌膀胱癌

项目摘要

To isolate human tumor antigens for immunotherapy of various cancers including esophageal, pancreatic and colon cancers, we applied the SEREX method, expression DNA cloning for the isolation of cDNAs encoding cancer proteins that could induce IgG antibody responses in patients with cancer. Using serum and cDNA library from a melanoma patient, a novel antigen KU-MEL1 was isolated. This antigen was not expressed in most normal tissues tested in the exception of cultured melanocytes, however, it was expressed in most melanoma cells as well as in various adonocarcinoma and squamous cell carcinoma. Using sera and cDNA library from patients with pancreatic cancer, a novel antigen KU-PAN1 was isolated. This antigen was not expressed in most normal tissues in the exception of testis, but expressed in some of the pancreatic, breast and colon cancers. Using sera and cDNA library from patients with esophageal cancer, previously isolated cancer-testis antigen, MAGE-A4, was isolated. MAGE-A4 was shown to be recognized by CD8+ T cells. Using sera and cDNA library from patients with colon cancer, EIF4 and AHNAK nucleoproteins were isolated. IgG antibodies specific for the antigens identified in the present study were detected in some sera from patients with various cancers, but not detected in sera from healthy individuals. Using sera and cDNA library from patients with bladder cancer, the protein homologous to ecalectin was isolated, and IgG antibody against this antigen was frequently detected in sera from patients with esophageal cancers. Therefore, these newly isolated tumor antigens may be useful for development of new diagnostic methods as well as immunotherapies for patients with various cancers.

为了分离用于各种癌症（包括食管癌、胰腺癌和结肠癌）的免疫治疗的人肿瘤抗原，我们应用SEREX方法、表达DNA克隆来分离编码能够在癌症患者中诱导IgG抗体应答的癌症蛋白的cDNA。从黑色素瘤患者血清和cDNA文库中分离到一种新的抗原KU-MEL 1。该抗原在除培养的黑素细胞外的大多数正常组织中不表达，然而，它在大多数黑色素瘤细胞以及各种腺癌和鳞状细胞癌中表达。利用胰腺癌患者血清和cDNA文库，分离到一种新的胰腺癌抗原KU-PAN 1。该抗原在除睾丸外的大多数正常组织中不表达，但在一些胰腺癌、乳腺癌和结肠癌中表达。利用食管癌患者的血清和cDNA文库，分离了先前分离的癌-睾丸抗原MAGE-A4。MAGE-A4显示被CD 8 + T细胞识别。利用大肠癌患者血清和cDNA文库，分离了EIF 4和AHNAK核蛋白。在本研究中鉴定的抗原的特异性IgG抗体在来自各种癌症患者的一些血清中检测到，但在来自健康个体的血清中未检测到。利用膀胱癌患者血清和cDNA文库，分离到与ecalectin同源的蛋白质，并在食管癌患者血清中检测到针对该抗原的IgG抗体。因此，这些新分离的肿瘤抗原可能有助于开发新的诊断方法以及各种癌症患者的免疫治疗。