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基于肿瘤相关碳水化合物抗原(TACAs)的抗肿瘤疫苗的最新进展。

Recent Advance in Tumor-associated Carbohydrate Antigens (TACAs)-based Antitumor Vaccines.

作者信息

Feng Danyang, Shaikh Abdul Sami, Wang Fengshan

机构信息

Key Laboratory of Chemical Biology of Natural Products (Ministry of education), Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Shandong University , Jinan 250012, Shandong, Peoples' Republic of China.

National Glycoengineering Research Center, Shandong University , Jinan 50012, Shandong, Peoples' Republic of ChinaChina.

出版信息

ACS Chem Biol. 2016 Apr 15;11(4):850-63. doi: 10.1021/acschembio.6b00084. Epub 2016 Mar 1.

Abstract

Cancer cells can be distinguished from normal cells by displaying aberrant levels and types of carbohydrate structures on their surfaces. These carbohydrate structures are known as tumor-associated carbohydrate antigens (TACAs). TACAs were considered as promising targets for the design of anticancer vaccines. Unfortunately, carbohydrates alone can only evoke poor immunogenicity because they are unable to induce T-cell-dependent immune responses, which is critical for cancer therapy. Moreover, immunotolerance and immunosuppression are easily induced by using natural occurring TACAs as antigens due to their endogenous property. This review summarizes the recent strategies to overcome these obstacles: (1) covalently coupling TACAs to proper carriers to improve immunogenicity, including clustered or multivalent conjugate vaccines, (2) coupling TACAs to T-cell peptide epitopes or the built-in adjuvant to form multicomponent glycoconjugate vaccines, and (3) developing vaccines based on chemically modified TACAs, which is combined with metabolic engineering of cancer cells.

摘要

癌细胞可通过其表面呈现异常水平和类型的碳水化合物结构与正常细胞区分开来。这些碳水化合物结构被称为肿瘤相关碳水化合物抗原(TACAs)。TACAs被认为是设计抗癌疫苗的有前景的靶点。不幸的是,仅碳水化合物本身只能引发较弱的免疫原性,因为它们无法诱导对癌症治疗至关重要的T细胞依赖性免疫反应。此外,由于天然存在的TACAs具有内源性,将其用作抗原很容易诱导免疫耐受和免疫抑制。本综述总结了最近克服这些障碍的策略:(1)将TACAs与合适的载体共价偶联以提高免疫原性,包括聚集或多价共轭疫苗;(2)将TACAs与T细胞肽表位或内置佐剂偶联以形成多组分糖共轭疫苗;(3)基于化学修饰的TACAs开发疫苗,并结合癌细胞的代谢工程。

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