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针对上皮性卵巢腺癌的单克隆抗体:与原发肿瘤异种移植物及培养细胞系的独特反应性。

Monoclonal antibodies to an epithelial ovarian adenocarcinoma: distinctive reactivity with xenografts of the original tumor and a cultured cell line.

作者信息

Baumal R, Law J, Buick R N, Kahn H, Yeger H, Sheldon K, Colgan T, Marks A

出版信息

Cancer Res. 1986 Aug;46(8):3994-4000.

PMID:3731068
Abstract

Four monoclonal antibodies (mAb) (8C, 10B, M2A, and M2D) were produced against the human epithelial ovarian adenocarcinoma cell line, HEY. The affinity constants of binding of the mAb to cultured HEY cells were 8 X 10(8) M-1 (M2D) and 10(9) M-1 (8C and 10B). mAb 8C reacted with a major glycoprotein of Mr 90,000 on the surface of HEY cells. The four mAb differed from previously reported mAb to epithelial ovarian adenocarcinomas on the basis of their reactivity with cultured ovarian adenocarcinoma cell lines using a cell-binding radioimmunoassay, and their staining of cryostat sections of various human normal and tumor tissues using an immunoperoxidase reaction. All four mAb reacted with s.c. tumors derived by injecting cultured HEY cells into thymectomized CBA/CJ mice. However, only two of the four mAb (8C and 10B) also reacted with s.c. tumors of the original HEY xenograft from which the cultured cell line was derived. In addition, mAb 8C and 10B reacted by immunoperoxidase staining with 2 and 4 different cases, respectively, of 11 epithelial ovarian adenocarcinomas examined. Cultured HEY cells were adapted to grow i.p. in BALB/c-nu/nu mice and the i.p. tumors retained their reactivity with the monoclonal antibodies. These tumor-bearing mice offer a useful model system for studying the potential of mAb, especially 8C and 10B, for the diagnosis and treatment of patients with peritoneal extension of epithelial ovarian adenocarcinomas.

摘要

制备了四种针对人上皮性卵巢腺癌细胞系HEY的单克隆抗体(mAb)(8C、10B、M2A和M2D)。这些单克隆抗体与培养的HEY细胞结合的亲和常数分别为8×10⁸ M⁻¹(M2D)和10⁹ M⁻¹(8C和10B)。单克隆抗体8C与HEY细胞表面一种分子量为90,000的主要糖蛋白发生反应。通过细胞结合放射免疫测定法检测这四种单克隆抗体与培养的卵巢腺癌细胞系的反应性,以及通过免疫过氧化物酶反应检测它们对各种人类正常组织和肿瘤组织冰冻切片的染色情况,结果表明这四种单克隆抗体与先前报道的针对上皮性卵巢腺癌的单克隆抗体不同。所有四种单克隆抗体都与通过将培养的HEY细胞注射到胸腺切除的CBA/CJ小鼠体内而产生的皮下肿瘤发生反应。然而,这四种单克隆抗体中只有两种(8C和10B)也与原始HEY异种移植瘤的皮下肿瘤发生反应,而该培养细胞系正是从该异种移植瘤中获得的。此外,在检测的11例上皮性卵巢腺癌中,单克隆抗体8C和10B分别通过免疫过氧化物酶染色与2例和4例不同病例发生反应。培养的HEY细胞经适应后可在BALB/c-nu/nu小鼠腹腔内生长,且腹腔内肿瘤保留了它们与单克隆抗体的反应性。这些荷瘤小鼠为研究单克隆抗体,尤其是8C和10B,在上皮性卵巢腺癌腹膜转移患者诊断和治疗中的潜力提供了一个有用的模型系统。

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