探索“甜蜜”疫苗的抗癌之路——基于合成寡糖的癌症免疫治疗

Exploring"Sweet"Vaccines——Synthetic Oligosaccharides for Cancer Immunotherapy

疫苗是人类与疾病斗争的有力武器。由于特征性糖蛋白和糖脂结构在恶性肿瘤细胞表面过度表达,肿瘤相关糖抗原可用于合成癌症候选疫苗。近年来,通过多步合成得到的寡糖-蛋白缀合物逐步进入临床实验。本文将重点介绍国际上研究工作的最新进展,包括候选疫苗分子的设计思路、寡糖抗原的结构与合成、疫苗载体蛋白、疫苗辅剂等。本文还将讨论寡糖合成,疫苗分子组成及临床前实验中面临的困难和可能的解决方案。

Vaccines provide a powerful tool to combat devastating human disease. The identification of distinct glycoprotein and glycolipid constructs that are over expressed on the cell surfaces of malignant cells has spurred intense research into exploiting these turnout-associated carbohydrate antigens （TACA） for the development of anticancer vaccines. Recently, some synthetic immunogenic carbohydrate-protein conjugates have been advanced to clinical trials. In this review, the progress of TACA based vaccine molecules will be demonstrated, which including design strategies of vaccines, structure and total synthesis of TACA molecules, vaccine carrier protein and vaccine adjuvants. Problems and solutions related to total synthesis of oligosaccharides, components of vaccine candidates and pre-clinical results are also discussed.