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一种具有体内抗肿瘤活性的新型鼠 IgG1 抗 Tn 单克隆抗体。

A new murine IgG1 anti-Tn monoclonal antibody with in vivo anti-tumor activity.

机构信息

Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden.

出版信息

Glycobiology. 2011 Aug;21(8):1097-107. doi: 10.1093/glycob/cwr048. Epub 2011 Apr 5.

Abstract

The Tn antigen (GalNAc α-O-Ser/Thr) is heterogeneously synthesized by a variety of tumors and contains an epitope defined by lectins and antibodies as a cluster of αGalNAc carbohydrates synthesized within a peptide sequence, which is rich in serine and/or threonine. The Tn antigen has been utilized as a target in vaccine experiments and also used as a biomarker for prognosis of different cancer forms. In this paper, we present a new monoclonal antibody, GOD3-2C4, with the clear hallmarks of an anti-Tn antibody. It was generated through somatic cell hybridization after immunization of a mouse with a tumor cell line and a Tn carrying mucin. The antibody recognizes synthetic Tn antigen and binds breast, colon, lung, ovarian and pancreas cancer. The GOD3-2C4 antibody has antibody-dependent cellular cytotoxicity activity against Jurkat cells in vitro, and for the first time, it can be shown that an anti-Tn antibody has a significant in vivo effect on a human cancer cell line grown as a xenograft in severe combined immunodeficiency mice.

摘要

Tn 抗原(GalNAcα-O-Ser/Thr)由多种肿瘤异质合成,含有一个由凝集素和抗体定义的表位,作为在富含丝氨酸和/或苏氨酸的肽序列内合成的αGalNAc 碳水化合物簇。Tn 抗原已被用作疫苗实验的靶点,也被用作不同癌症形式预后的生物标志物。在本文中,我们介绍了一种新的单克隆抗体 GOD3-2C4,它具有明确的抗-Tn 抗体特征。它是通过用肿瘤细胞系和携带 Tn 的粘蛋白免疫的小鼠进行体细胞杂交产生的。该抗体识别合成的 Tn 抗原,并与乳腺癌、结肠癌、肺癌、卵巢癌和胰腺癌结合。GOD3-2C4 抗体在体外对 Jurkat 细胞具有抗体依赖性细胞毒性活性,并且首次可以表明抗-Tn 抗体对在严重联合免疫缺陷小鼠中作为异种移植物生长的人癌细胞系具有显著的体内作用。

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