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针对神经节苷脂GD2及其内酯上抗原决定簇的单克隆抗体。胶质瘤和神经母细胞瘤的标志物。

Monoclonal antibodies against epitopes on ganglioside GD2 and its lactones. Markers for gliomas and neuroblastomas.

作者信息

Bosslet K, Mennel H D, Rodden F, Bauer B L, Wagner F, Altmannsberger A, Sedlacek H H, Wiegandt H

机构信息

Research Laboratories of Behringwerke AG, Marburg/Lahn, Federal Republic of Germany.

出版信息

Cancer Immunol Immunother. 1989;29(3):171-8. doi: 10.1007/BF00199992.

Abstract

Monoclonal antibodies (mAbs) BW 625 and BW 704, of the IgG3 isotype, bound to immunochemically indistinguishable epitopes on ganglioside II3(Neu-Ac)2-GgOse3-Cer. Despite this fact the mAbs showed a differential binding pattern on human glioma cell lines i.e. immunohistochemical data indicate that the detected epitopes are not identical. Furthermore, either mAb is able to mediate the antibody-dependent cellular cytotoxicity reaction (ADCC) and the human-complement-dependent cytotoxicity reaction (CDC) with epitope-expressing tumor cells. All cryopreserved tissue specimens from gliomas and neuroblastomas were immunohistochemically stained, whereas the other small round cell tumors of childhood, as well as melanomas and small-cell lung carcinomas, were essentially negative. Positive staining of normal cryopreserved tissues was restricted to amyelinic axons, Hassal's bodies and some connective tissue fibers in thymus and the tegumentary epithelium of skin. The high selectivity of mAb BW 704 for gliomas and neuroblastomas, the lack of cross-reactivity with major tissues and the strong ADCC and CDC potential argue for the use of mAb BW 704 in immunotherapy of neuroblastomas and gliomas.

摘要

IgG3同种型的单克隆抗体(mAb)BW 625和BW 704与神经节苷脂II3(Neu-Ac)2-GgOse3-Cer上免疫化学上无法区分的表位结合。尽管如此,这些单克隆抗体在人胶质瘤细胞系上显示出不同的结合模式,即免疫组织化学数据表明检测到的表位并不相同。此外,任何一种单克隆抗体都能够介导与表达表位的肿瘤细胞的抗体依赖性细胞毒性反应(ADCC)和人补体依赖性细胞毒性反应(CDC)。对来自胶质瘤和神经母细胞瘤的所有冷冻保存组织标本进行了免疫组织化学染色,而儿童期的其他小圆形细胞肿瘤以及黑色素瘤和小细胞肺癌基本上呈阴性。正常冷冻保存组织的阳性染色仅限于无髓鞘轴突、哈氏小体以及胸腺中的一些结缔组织纤维和皮肤的被覆上皮。单克隆抗体BW 704对胶质瘤和神经母细胞瘤具有高选择性,与主要组织无交叉反应性,且具有强大的ADCC和CDC潜力,这表明单克隆抗体BW 704可用于神经母细胞瘤和胶质瘤的免疫治疗。

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