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一种针对人胚胎癌的单克隆抗体的研制与特性分析

Development and characterization of a monoclonal antibody to human embryonal carcinoma.

作者信息

Khazaeli M B, Beierwaltes W H, Pitt G S, Kabza G A, Rogers K J, LoBuglio A F

出版信息

J Urol. 1987 Jun;137(6):1295-9. doi: 10.1016/s0022-5347(17)44486-7.

Abstract

A monoclonal anti-testicular carcinoma antibody was obtained via the somatic cell fusion technique by immunization of BALB/c mice with freshly prepared single cell suspension from a patient with testicular embryonal carcinoma with choriocarcinoma components. The hybridoma supernates were screened against the testicular carcinoma cells used in the immunization as well as normal mononuclear white blood cells isolated from the same patient. An antibody (5F9) was selected which bound to fresh tumor cells from two patients with embryonal testicular carcinoma and failed to bind to fresh tumor cells from 24 patients (2 seminoma, 2 melanoma, 3 neck, 2 esophageal, 1 ovarian, 3 colon, 1 prostate, 2 breast, 1 liposarcoma, 3 endometrial, 1 kidney, 1 adrenal, 1 larynx and 1 bladder tumors) or cell suspensions prepared from normal liver, lung, spleen, ovary, testes, kidney, red blood cells or white blood cells. The antibody was tested for its binding to several well established cancer cell lines, and was found to bind to the BeWo human choriocarcinoma and two human embryonal carcinoma cell lines. The antibody did not react with 22 other cell lines or with hCG. The antibody was labeled with 131I and injected into nude mice bearing BeWo tumors and evaluated for tumor localization by performing whole body scans with a gamma camera 5 days later. Six mice injected with the antibody showed positive tumor localization without the need for background subtraction while six mice injected with MOPC-21, a murine myeloma immunoglobulin, demonstrated much less tumor localization. Tissue distribution studies performed after scanning showed specific tumor localization (8:1 tumor: muscle) for the monoclonal antibody and no specific localization for MOPC-21. This antibody thus has selective reactivity with the surface of tumor cells from embryonal carcinoma (testicle) and choriocarcinoma both in vitro and in vivo.

摘要

通过体细胞融合技术,用一名患有睾丸胚胎癌伴绒毛膜癌成分患者的新鲜单细胞悬液免疫BALB/c小鼠,获得了一种单克隆抗睾丸癌抗体。针对用于免疫的睾丸癌细胞以及从同一患者分离的正常单核白细胞,对杂交瘤培养上清液进行筛选。选择了一种抗体(5F9),它能与两名胚胎性睾丸癌患者的新鲜肿瘤细胞结合,但不与24名患者(2例精原细胞瘤、2例黑色素瘤、3例颈部肿瘤、2例食管癌、1例卵巢癌、3例结肠癌、1例前列腺癌、2例乳腺癌、1例脂肪肉瘤、3例子宫内膜癌、1例肾癌、1例肾上腺癌、1例喉癌和1例膀胱癌)的新鲜肿瘤细胞或由正常肝脏、肺、脾、卵巢、睾丸、肾脏、红细胞或白细胞制备的细胞悬液结合。测试了该抗体与几种已建立的癌细胞系的结合情况,发现它能与BeWo人绒毛膜癌细胞系和两个人胚胎癌细胞系结合。该抗体不与其他22种细胞系或hCG反应。用131I标记该抗体,注射到荷BeWo肿瘤的裸鼠体内,5天后用γ相机进行全身扫描评估肿瘤定位。注射抗体的6只小鼠显示出阳性肿瘤定位,无需进行背景扣除,而注射鼠骨髓瘤免疫球蛋白MOPC-21的6只小鼠显示出的肿瘤定位要少得多。扫描后进行的组织分布研究表明,单克隆抗体具有特异性肿瘤定位(肿瘤:肌肉为8:1),而MOPC-21没有特异性定位。因此,该抗体在体外和体内均与胚胎癌(睾丸)和绒毛膜癌的肿瘤细胞表面具有选择性反应性。

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