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单克隆抗体和合成肿瘤相关糖缀合物在人类癌症中Thomsen-Friedenreich样和Tn样抗原表达研究中的应用

Monoclonal antibodies and synthetic tumor-associated glycoconjugates in the study of the expression of Thomsen-Friedenreich-like and Tn-like antigens on human cancers.

作者信息

Longenecker B M, Willans D J, MacLean G D, Selvaraj S, Suresh M R, Noujaim A A

出版信息

J Natl Cancer Inst. 1987 Mar;78(3):489-96.

PMID:3469463
Abstract

Synthetic carbohydrate haptens, which are conjugated to carrier human serum albumin molecules [synthetic tumor-associated glycoconjugates (S-TAGs)], were used to immunize mice for monoclonal antibody (MoAb) production. Two of the S-TAGs were composed of haptens related to the Thomsen-Friedenreich (TF) antigen, and their structures are beta Gal(1----3)-beta GalNAc (TF-beta) and beta Gal(1----3) alpha GalNAc (TF-alpha) (Gal = galactose; GaNAc = N-acetylgalactosamine). The third S-TAG was made up of Tn hapten groups of the structure alpha GalNAc-O-serine. MoAbs specific for TF-alpha and Tn were able to be generated. All MoAbs generated against TF-beta cross-reacted with TF-alpha but not with Tn. None of the TF-alpha-specific MoAbs reacted with human carcinomas, whereas several TF-beta and Tn MoAbs were found to react with most human lung, colon, and breast carcinomas. It is believed that this is the first report of the use of synthetic carbohydrate cancer antigens for the production of anticancer MoAbs.

摘要

将合成碳水化合物半抗原与载体人血清白蛋白分子偶联(合成肿瘤相关糖缀合物[S-TAGs]),用于免疫小鼠以产生单克隆抗体(MoAb)。其中两种S-TAGs由与汤姆森-弗里德赖希(TF)抗原相关的半抗原组成,其结构为βGal(1→3)-βGalNAc(TF-β)和βGal(1→3)αGalNAc(TF-α)(Gal = 半乳糖;GaNAc = N-乙酰半乳糖胺)。第三种S-TAG由结构为αGalNAc-O-丝氨酸的Tn半抗原基团组成。能够产生针对TF-α和Tn的特异性MoAb。所有针对TF-β产生的MoAb均与TF-α交叉反应,但不与Tn交叉反应。没有一种TF-α特异性MoAb与人癌反应,而发现几种TF-β和Tn MoAb与大多数人肺癌、结肠癌和乳腺癌反应。据信,这是关于使用合成碳水化合物癌症抗原生产抗癌MoAb的首次报道。

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