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针对卵巢癌腹水细胞表面表达的人上皮分化抗原的小鼠单克隆抗体。

Mouse monoclonal antibodies to human epithelial differentiation antigens expressed on the surface of ovarian carcinoma ascites cells.

作者信息

Mattes M J, Look K, Furukawa K, Pierce V K, Old L J, Lewis J L, Lloyd K O

机构信息

Memorial Sloan-Kettering Cancer Center, New York, New York 10021.

出版信息

Cancer Res. 1987 Dec 15;47(24 Pt 1):6741-50.

PMID:3677104
Abstract

Four different human epithelial differentiation antigens (MT179, MW162, MW207, and MX35) have been defined by mouse monoclonal antibodies obtained from mice immunized with either an ovarian carcinoma cell line or fresh ovarian carcinoma cells. In an attempt to identify tissue-specific antigens restricted to ovarian epithelial cells, sections of a benign ovarian cyst were used as the initial target for screening hybridoma supernatants. The distribution of the antigens detected by these monoclonal antibodies was determined on frozen sections of 24 normal tissues and on 103 cultured cell lines of various histological types. In spite of the method used to select these monoclonal antibodies, they all reacted to some degree with normal epithelial cells in tissues other than ovary. All antibodies were unreactive with nonepithelial cells in frozen sections. These antibodies also reacted with frozen sections of most or all fresh ovarian carcinomas and benign ovarian cysts. All antibodies were unreactive with ABH, Lewis blood group-related antigens and appeared to be different in specificity from previously described well-characterized antigens of ovarian carcinoma cells. MW162 was characterized as a high-molecular-weight mucin-like molecule, and the determinant recognized is probably carbohydrate in nature. MW207 was identified as a Mr 37,000 protein. These monoclonal antibodies and 24 other previously derived antibodies that react with epithelial differentiation antigens were tested for reactivity with the surface of fresh ovarian carcinoma ascites cells and for nonreactivity with normal mesothelial cells. This assay was designed to select monoclonal antibodies that might be effective agents for i.p. therapy or radioimmunodetection of human ovarian carcinoma. Five antibodies with the desired specificity were selected; these were the four new antibodies described herein and MH99, which was characterized previously and recognizes a glycoprotein having Mr 38,000 and 29,000 subunits. The degree of heterogeneity of antigen expression on ascites carcinoma cell was dependent on the particular antigen being examined and was related to the biochemical nature of the antigen. In particular, most ABH and Lewis blood group-related antigens showed a striking degree of heterogeneity.

摘要

通过用卵巢癌细胞系或新鲜卵巢癌细胞免疫小鼠获得的小鼠单克隆抗体,已鉴定出四种不同的人上皮分化抗原(MT179、MW162、MW207和MX35)。为了鉴定仅限于卵巢上皮细胞的组织特异性抗原,将良性卵巢囊肿切片用作筛选杂交瘤上清液的初始靶标。在24种正常组织的冰冻切片和103种不同组织学类型的培养细胞系上,测定了这些单克隆抗体所检测抗原的分布。尽管用于选择这些单克隆抗体的方法不同,但它们在一定程度上都与卵巢以外组织中的正常上皮细胞发生反应。所有抗体在冰冻切片中与非上皮细胞均无反应。这些抗体也与大多数或所有新鲜卵巢癌和良性卵巢囊肿的冰冻切片发生反应。所有抗体与ABH、Lewis血型相关抗原均无反应,且在特异性上似乎与先前描述的特征明确的卵巢癌细胞抗原不同。MW162被鉴定为一种高分子量粘蛋白样分子,所识别的决定簇可能本质上是碳水化合物。MW207被鉴定为一种分子量为37,000的蛋白质。测试了这些单克隆抗体以及其他24种先前获得的与上皮分化抗原发生反应的抗体与新鲜卵巢癌腹水细胞表面的反应性以及与正常间皮细胞的无反应性。该试验旨在选择可能成为人卵巢癌腹腔内治疗或放射免疫检测有效试剂的单克隆抗体。选择了五种具有所需特异性的抗体;它们是本文所述的四种新抗体以及MH99,MH99先前已被鉴定,可识别一种具有分子量为38,000和29,000亚基的糖蛋白。腹水癌细胞上抗原表达的异质性程度取决于所检测的特定抗原,并与抗原的生化性质有关。特别是,大多数ABH和Lewis血型相关抗原表现出显著程度的异质性。

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Cancer Res. 1987 Dec 15;47(24 Pt 1):6741-50.
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