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人IgM单克隆抗GD2抗体:对人黑色素瘤异种移植瘤的反应性。

Human IgM monoclonal anti-GD2 antibody: reactivity to a human melanoma xenograft.

作者信息

Katano M, Saxton R E, Tsuchida T, Irie R F

出版信息

Jpn J Cancer Res. 1986 Jun;77(6):584-94.

PMID:3089993
Abstract

The cell membranes of human melanoma express a tumor-associated ganglioside, GD2. We previously established a human melanoma cell line, M14-A, that metastasizes to the lung, liver, skin, lymph nodes, and abdominal organs of nude mice in addition to forming ascites and pleural effusions. We also reported the successful in vitro production of human IgM monoclonal antibody to GD2. In the present study, we evaluated the GD2 expression of human melanoma cells at the primary and metastatic sites and their reactivity to human monoclonal anti-GD2 antibody in vivo. GD2 was expressed strongly on the melanoma cells from both primary and metastatic sites, except for cells from pleural effusions and ascites. When M14-A-bearing nude mice received systemic injections of the human monoclonal antibody, the anti-GD2 titer in the sera was reduced markedly at 2 hours, whereas the reduction was minimal in sera from tumor-free mice and mice bearing GD2-negative human M24 cells. The immune adherence test confirmed that antibody was fixed on cells of primary subcutaneous M14-A tumors and on their metastases to liver, lung, abdominal organs and skin. These results suggest that this large molecule protein can penetrate the blood-tumor barrier and bind immunologically to antigen-positive melanoma cells in vivo.

摘要

人类黑色素瘤的细胞膜表达一种肿瘤相关神经节苷脂,GD2。我们之前建立了一种人类黑色素瘤细胞系,M14 - A,它除了能形成腹水和胸腔积液外,还会转移至裸鼠的肺、肝、皮肤、淋巴结和腹部器官。我们还报道了成功在体外生产出针对GD2的人IgM单克隆抗体。在本研究中,我们评估了人类黑色素瘤细胞在原发部位和转移部位的GD2表达情况以及它们在体内与人抗GD2单克隆抗体的反应性。除了来自胸腔积液和腹水的细胞外,原发部位和转移部位的黑色素瘤细胞均强烈表达GD2。当携带M14 - A的裸鼠接受人单克隆抗体的全身注射后,血清中的抗GD2滴度在2小时时显著降低,而在无瘤小鼠和携带GD2阴性人M24细胞的小鼠血清中,这种降低则微乎其微。免疫黏附试验证实抗体固定在原发性皮下M14 - A肿瘤细胞及其转移至肝、肺、腹部器官和皮肤的细胞上。这些结果表明,这种大分子蛋白能够穿透血 - 肿瘤屏障,并在体内与抗原阳性的黑色素瘤细胞发生免疫结合。

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