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针对结直肠癌血清抗原的单克隆抗体的制备。

Production of monoclonal antibodies to serum antigens in colorectal carcinoma.

作者信息

Teh J G, Thompson C H, McKenzie I F

机构信息

Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.

出版信息

J Immunol Methods. 1988 May 25;110(1):101-9. doi: 10.1016/0022-1759(88)90088-9.

Abstract

Two monoclonal antibodies (mAb) to colorectal cancer were produced using a novel immunization technique. This involved immunizing mice with whole serum obtained from patients with cancer of the colon (three with metastatic disease) and resulted in antibodies which were reactive with colonic tumor tissue by immunoperoxidase testing. Two mAbs (O-1, I-1) were isolated which were non-reactive with normal tissue and with tissues obtained from subjects with benign disease but were reactive with 34/50 (formalin-fixed) colon carcinoma specimens. Further testing on cell lines and other malignant tumors suggested both mAbs detect carcinoembryonic antigen (CEA) as their reactivities were similar to a known anti-CEA antibody, and they reacted with CEA in a solid-phase radioimmunoassay. The two mAbs were found to react with the same or closely associated epitopes on CEA by competitive tests. As the anti-CEA antibodies were made to serum (rather than tissue) CEA, it was possible that unique, highly specific mAb has been produced, particularly as there was a selective reaction of the mAbs for malignant but not normal tissues. A serum test with mAb I-1 was developed which detected raised serum CEA levels in 3/24 patients with benign colonic lesions, 7/19 patients with pancreatic cancer, 5/25 patients with colonic cancer but not in 20 normal individuals. There was direct correlation between these results and a commercially available CEA test kit.

摘要

采用一种新型免疫技术制备了两种针对结直肠癌的单克隆抗体(mAb)。这包括用从结肠癌患者(3例有转移性疾病)获得的全血清免疫小鼠,通过免疫过氧化物酶检测产生与结肠肿瘤组织反应的抗体。分离出两种单克隆抗体(O-1、I-1),它们与正常组织以及从患有良性疾病的受试者获得的组织无反应,但与34/50例(福尔马林固定)结肠癌标本有反应。对细胞系和其他恶性肿瘤的进一步检测表明,这两种单克隆抗体均检测到癌胚抗原(CEA),因为它们的反应性与已知的抗CEA抗体相似,并且它们在固相放射免疫测定中与CEA发生反应。通过竞争性试验发现这两种单克隆抗体与CEA上相同或紧密相关的表位发生反应。由于抗CEA抗体是针对血清(而非组织)CEA制备的,因此有可能产生了独特的、高度特异性的单克隆抗体,特别是因为这些单克隆抗体对恶性组织而非正常组织有选择性反应。开发了一种使用单克隆抗体I-1的血清检测方法,该方法在24例良性结肠病变患者中有3例、19例胰腺癌患者中有7例、25例结肠癌患者中有5例检测到血清CEA水平升高,但在20名正常个体中未检测到。这些结果与市售的CEA检测试剂盒之间存在直接相关性。

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