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[小鼠单克隆抗体K2.7对人肾细胞癌的肾癌特异性抗肿瘤活性]

[Renal cancer specific antitumor activities of a mouse monoclonal antibody K2.7 to human renal cell carcinoma].

作者信息

Kinouchi T, Kotake T

机构信息

Department of Urology, Center for Adult Diseases, Osaka.

出版信息

Hinyokika Kiyo. 1992 Nov;38(11):1325-31.

PMID:1485589
Abstract

We have prepared a mouse monoclonal antibody (mAb) K2.7 (IgG3) by immunizing mice with renal cancer cell (RCC) line OS-RC-2. In a serological analysis by protein A assay, 25 out of 31 RCC lines reacted with the mAb K2.7 but none of the 50 other cell lines from different organs except for 2 cell lines did. In immunohistological analysis by indirect immunoperoxidase assay, 66 out of 72 renal cancer tissues showed positive staining. Metastatic lesions of renal cancers also reacted similarly to the primary lesion. Some restricted normal tissues including tubules of normal kidney showed positive staining. Specific antitumor activities of mAb K2.7 against RCC lines were investigated in vitro by complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC) assays. In CDC assay, all of the 9 RCC lines were killed by mAb K2.7 and normal human serum, and killing activities of mAb K2.7 presumably depend on the number of antibody molecules bound to the cell surface. Sera from 9 patients with renal cancers including low and high stages showed the same killing activities to 3 RCC lines as normal human serum. In the ADCC assay, peripheral leukocytes (PBLs) from 4 healthy donors showed strong killing activities to RCC lines. Killing activity differed with the individual. PBLs from the same 9 patients as in the CDC assay showed significantly positive killing activity against 3 RCC lines. These findings suggest the usefulness of mAb K2.7 for the specific immunotherapy of renal cancer.

摘要

我们用肾癌细胞系OS-RC-2免疫小鼠,制备了一种小鼠单克隆抗体(mAb)K2.7(IgG3)。在通过蛋白A检测进行的血清学分析中,31个肾癌细胞系中有25个与mAb K2.7反应,但除2个细胞系外,来自不同器官的其他50个细胞系均无反应。在通过间接免疫过氧化物酶检测进行的免疫组织学分析中,72个肾癌组织中有66个显示阳性染色。肾癌转移灶与原发灶的反应相似。一些受限的正常组织,包括正常肾的小管,显示阳性染色。通过补体依赖性细胞毒性(CDC)和抗体依赖性细胞介导的细胞毒性(ADCC)检测,在体外研究了mAb K2.7对肾癌细胞系的特异性抗肿瘤活性。在CDC检测中,9个肾癌细胞系均被mAb K2.7和正常人血清杀死,mAb K2.7的杀伤活性可能取决于与细胞表面结合的抗体分子数量。9例包括低分期和高分期的肾癌患者的血清对3个肾癌细胞系的杀伤活性与正常人血清相同。在ADCC检测中,4名健康供体的外周血白细胞(PBL)对肾癌细胞系显示出强烈的杀伤活性。杀伤活性因个体而异。与CDC检测中相同的9例患者的PBL对3个肾癌细胞系显示出显著的阳性杀伤活性。这些发现表明mAb K2.7对肾癌的特异性免疫治疗有用。

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