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抗Thomsen-Friedenreich抗原(anti-TF-Ag)在癌症治疗中的潜力。

Anti-Thomsen-Friedenreich-Ag (anti-TF-Ag) potential for cancer therapy.

作者信息

Almogren Adel, Abdullah Julia, Ghapure Kshipra, Ferguson Kimiko, Glinsky Vladislav V, Rittenhouse-Olson Kate

机构信息

Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

出版信息

Front Biosci (Schol Ed). 2012 Jan 1;4(3):840-63. doi: 10.2741/s304.

Abstract

Thomsen-Friedenreich antigen (TF-Ag) is the disaccharide (Gal beta1-3 GalNAc alpha), which is also known as the core 1 structure. The presence of this disaccharide on the surface of approximately 90 percent of carcinomas is due to altered glycosylation in these tumors. TF-Ag plays a role in the adhesive properties of tumor cells involved in metastasis. Treatment of mice with JAA-F11, a monoclonal antibody to TF-Ag alpha inhibited lung metastasis and improved prognosis in a mouse breast cancer model. The presence of naturally occurring antibodies to TF-Ag in cancer patients is related to improved prognosis. The pancarcinoma expression of TF-Ag, combined with the evidence of a mechanistic role for TF-Ag in cancer spread, show that this target would have clinical utility. The presence of naturally occurring antibody to TF-Ag indicates that increasing the anti-TF-Ag antibody would be safe for the cancer patient and indicates that tolerance would not have to be broken to create this immune response. Finally, the prognostic improvements seen clinically and in animal models indicate that this is an important vaccine target.

摘要

汤姆森-弗里德赖希抗原(TF-Ag)是二糖(半乳糖β1-3 N-乙酰半乳糖胺α),也被称为核心1结构。约90%的癌表面存在这种二糖是由于这些肿瘤中糖基化改变所致。TF-Ag在参与转移的肿瘤细胞黏附特性中起作用。用JAA-F11(一种针对TF-Agα的单克隆抗体)治疗小鼠,在小鼠乳腺癌模型中抑制了肺转移并改善了预后。癌症患者中天然存在针对TF-Ag的抗体与预后改善有关。TF-Ag的全癌表达,结合TF-Ag在癌症扩散中起机制性作用的证据,表明该靶点具有临床应用价值。天然存在针对TF-Ag的抗体表明增加抗TF-Ag抗体对癌症患者是安全的,并且表明不必打破耐受性来产生这种免疫反应。最后,临床和动物模型中观察到的预后改善表明这是一个重要的疫苗靶点。

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