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甲胎蛋白特异性抗体的纯化及其对癌细胞的免疫作用。

Purification of specific antibody to alpha-foetoprotein and its immunological effect on cancer cells.

作者信息

Hirai H, Tsukada Y, Hara A, Hibi N, Nishi S, Wepsic H T, Koji T, Ishii N

出版信息

J Chromatogr. 1981 Oct 23;215:195-210. doi: 10.1016/s0021-9673(00)81399-0.

Abstract

Human of rat alpha-foetoprotein (AFP) was highly purified from ascitic fluid or serum of hepatoma bearers. The purification was carried out mainly by means of immunoadsorbent chromatography using Sepharose coupled to specific anti-AFP antibody with BrCN activation, and by Sephadex gel filtration. Horses were immunized with the purified AFP and the specific antibody was isolated from the antiserum by means of an immunoadsorbent coupled to purified AFP. The specific antibody was found to bind specifically with AFP-producing tumour cells. The antibody was applied for radio immunodetection of the tumour. 125I-labelled antibody was administered to patients or rats with hepatoma, and radioactivity localized in the tumours was scintiscanned with a scintillation camera. In this way, the location of the tumour was detected in about 50% of the hepatoma bearers. The cytotoxicity of the antibody was clearly demonstrated both in vitro and in vivo in animal experiments. The antibody was administered to patients with advanced hepatoma. Although no improvement of the disease was demonstrated, serum AFP levels decreased greatly and in some cases low AFP levels were maintained for long periods suggesting that the antibody suppressed AFP-producing hepatoma cells. No significant side effects were observed in patients who had been administered with the horse antibody.

摘要

从肝癌患者的腹水或血清中高度纯化人源大鼠甲胎蛋白(AFP)。纯化主要通过使用经溴化氰活化后偶联特异性抗AFP抗体的琼脂糖凝胶进行免疫吸附层析,以及葡聚糖凝胶过滤来实现。用纯化的AFP免疫马匹,并通过偶联纯化AFP的免疫吸附剂从抗血清中分离出特异性抗体。发现该特异性抗体能与产生AFP的肿瘤细胞特异性结合。该抗体用于肿瘤的放射免疫检测。将125I标记的抗体给予肝癌患者或大鼠,并用闪烁照相机对肿瘤部位的放射性进行闪烁扫描。通过这种方法,在约50%的肝癌患者中检测到了肿瘤的位置。在动物实验中,该抗体的细胞毒性在体外和体内均得到了明确证实。将该抗体给予晚期肝癌患者。尽管未显示疾病有所改善,但血清AFP水平大幅下降,在某些情况下,低AFP水平长期维持,提示该抗体抑制了产生AFP的肝癌细胞。接受马抗体治疗的患者未观察到明显的副作用。

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